Evolution of Gene Regulatory Networks Controlling Body Plan Development

A counteracting locus control region from beyond the 5' end represses posterior hox genes in anterior cells of the early limb bud, allowing their expression only in posterior limb bud cells.

“the posterior hox genes are repressed by a counteracting locus control region operating from beyond the 5' end of the complex in the anterior cells of the early limb bud, allowing expression of these genes only in the posterior limb bud cells.”

• cites Herault et al., 1999 sourceDisputed

  The Discussion (page unavailable) describes the element 5′ of HoxD as a digit enhancer, not a repressor of anterior limb-bud expression. Its proposed counteracting controls govern expression in digits versus forearm along the proximodistal axis; the paper does not describe a 5′ locus control region restricting posterior Hox genes to posterior limb-bud cells. (LLM, conf=0.85)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites Herault et al., 1998 sourceNot checked — no full text of the source
• cites Kmita et al., 2000 sourcePartly supported

  The ‘Hoxb1 in digits and genitalia’ section (page unavailable) describes a remote regulatory sequence affecting Hox gene expression in limbs, and ‘Expression of Hoxb1 inside and outside of HoxD’ reports a posterior-Hoxd-like limb expression pattern. But the paper does not establish that a counteracting locus control region beyond the 5′ end represses posterior Hox genes specifically in anterior cells of the early limb bud. Its discussion of silencing concerns other developmental contexts and cautions against a universal repression model. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

The underlying genomic event for pelvic spine reduction is deletion of a cis-regulatory module controlling pitx1 expression in pelvic buds during larval development.

“The underlying genomic event turns out to be deletion of a cis-regulatory module which controls expression of the pitx1 regulatory gene in the pelvic buds during larval development (Chan et al., 2010).”

• cites Chan et al., 2010 sourceSupported

Mobile elements could have provided a major mechanism of gene regulatory network evolution.

“In summary, as previously speculated (Britten and Davidson, 1971), mobile elements could have provided a major mechanism of GRN evolution.”

• cites Britten and Davidson, 1971 sourcePartly supported

  In “Proposals for the Origin of Evolutionary Novelty” (pp. 124–126), the paper speculates that genomic rearrangements could construct new regulatory networks, including by moving regulatory sequences to new locations. That supports the proposed link to regulatory-network evolution, but the passages describe chromosomal rearrangements and repetitive sequences, not mobile elements specifically as a major mechanism. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Introducing the cloned cis-regulatory module upstream of Pitx1 coding sequence into reduced spine fish rescued the spineless phenotype.

“when this cis-regulatory module was cloned upstream of a sequence encoding the Pitx1 protein and introduced into reduced spine fish, it rescued the spineless phenotype.”

• cites Chan et al., 2010 sourceSupported

The arrangement, spacing, and number of target sites are relatively insignificant.

“The arrangement, spacing, and number of these sites is relatively insignificant (Balhoff and Wray, 2005; Cameron and Davidson, 2009; Dermitzakis et al., 2003; Liberman and Stathopoulos, 2009; Ludwig et al., 2000; Walters et al., 2008).”

• cites Balhoff and Wray, 2005 sourceNot checked — no full text of the source
• cites Cameron and Davidson, 2009 sourceSupported
• cites Dermitzakis et al., 2003 sourcePartly supported

  The Introduction says regulatory function can persist despite structural reorganization caused by binding-site gains and losses. The section “Predicting the Pattern of Binding Site Evolution” similarly suggests that some predicted sites can be gained or lost without strong effects on gene regulation. Neither passage establishes that site arrangement, spacing, and number are generally insignificant; the latter finding is limited to predicted sites with less essential roles. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Short legs in dog breeds such as dachshunds and basset hounds are due to a retrogene encoding FGF4, inserted and evidently controlled by cis-regulatory elements carried in non-LTR transposons.

“short legs in dog breeds such as dachshunds and basset hounds is due to a retrogene encoding FGF4, inserted and evidently controlled by cis-regulatory elements carried in non-LTR transposons (Parker et al., 2009).”

• cites Parker et al., 2009 sourceSupported

Recent studies of Drosophila species have revealed cis-regulatory sequence microevolution underlying adaptive external trait variation.

“Recent studies that focused on the adaptive evolution of external traits in and among Drosophila species have revealed processes of cis-regulatory sequence microevolution.”

• cites Gompel et al., 2005 sourceNot checked — no full text of the source
• cites Rokas and Carroll, 2006 sourceCould not verify

  The section ‘Why Hundreds of Genes Might Not Suffice’ discusses positive selection and amino acid substitutions, while the Drosophila references concern protein evolution and genomic data. Searches for cis-regulatory microevolution and regulatory changes in external traits found no passage addressing the claimed finding; page numbers are unavailable in our copy. (LLM, conf=0.74)

  Experimental — accuracy not yet measured
• cites Rebeiz et al., 2009 sourceSupported

Excess Shh indirectly promotes apoptosis in lens and retina.

“Also, excess Shh indirectly promotes apoptosis in lens and retina.”

• cites Jeffery, 2009 sourceSupported

Evolutionary changes in any pleiotropically active gene, as are most regulatory genes, will generally target specific cis-regulatory modules.

“it predicts that evolutionary changes in any pleiotropically active gene, as are most regulatory genes, will generally target specific cis-regulatory modules”

• cites Chan et al., 2010 sourcePartly supported

  The Discussion reports adaptive change centered on the tissue-specific Pel enhancer rather than the Pitx1 coding region, and ‘A small enhancer drives pelvic expression of Pitx1’ shows that this enhancer acts in one of several tissues where Pitx1 is expressed. This supports Pitx1 as an example, but the paper does not predict that evolutionary changes in any pleiotropic gene will generally target specific cis-regulatory modules, or state that most regulatory genes are pleiotropic. Page numbers are unavailable in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Miller et al., 2007 sourceNot checked — no full text of the source
• cites Prud'homme et al., 2006 sourceNot checked — no full text of the source

tbx5 is regulated differently during heart formation in reptiles than in birds and mammals, a Class-level difference.

“the tbx5 gene, deeply embedded in the vertebrate heart formation GRN (for review Davidson, 2006), turns out to be regulated differently during heart formation in reptiles than in birds and mammals, a Class-level difference.”

• cites Koshiba-Takeuchi et al., 2009 sourcePartly supported

  The passage on ventricular patterning (page unavailable) reports broad early Tbx5 expression in turtle and anole hearts, unlike the early restriction in chick and mouse. But it also reports a later left–right gradient in turtles and distinguishes avian/crocodilian hearts from the reptilian hearts studied. The evidence supports a difference in developmental expression patterns, not a uniform difference across the entire reptile class. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Excess Shh causes expression of vax1 and pax2a, which interfere with pax6 expression and the downstream pax6 ocular patterning subcircuit.

“excess Shh causes expression of transcription repressors (vax1 and pax2a) which interfere with pax6 expression and thus the downstream pax6 ocular patterning subcircuit (Jeffery, 2009; Yamamoto et al., 2004) (Baumer et al., 2002).”

• cites Jeffery, 2009 sourcePartly supported

  In “Candidate Gene Analysis” (page unavailable), the review reports that increased Shh downregulates pax6 and that cavefish embryos show both reduced pax6 and overexpressed pax2a and vax1. It describes antagonism among these transcription factors, but does not establish that excess Shh causes pax2a and vax1 expression or describe a downstream pax6 ocular-patterning subcircuit. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Yamamoto et al., 2004 sourceNot checked — no full text of the source
• cites Baumer et al., 2002 sourceNot checked — no full text of the source

Early hoxd expression in the tetrapod limb bud is controlled not only by local enhancers but also by distant regulatory regions outside the hox gene clusters.

“early expression in the tetrapod limb bud is controlled not only by local enhancers but also by distant regulatory regions located outside the hox gene clusters.”

• cites Herault et al., 1999 sourcePartly supported

  The Introduction (page unavailable) describes a distant enhancer, likely upstream of the HoxD complex, that drives expression in the distal digit domain. But the Discussion (page unavailable) concerns late limb expression and says nearby gene-specific elements may not significantly affect it. The paper therefore does not establish the claimed combination of local enhancers and distant regions controlling early limb-bud expression. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Herault et al., 1998 sourceNot checked — no full text of the source
• cites Kmita et al., 2000 sourcePartly supported

  In “Hoxb1 in digits and genitalia” (page unavailable), the paper argues that a remote enhancer or regulatory sequence can regulate limb expression, rather than nearby sequences. “Expression of Hoxb1 inside and outside of HoxD” reports this pattern in distal limb buds from day 10.5, but the copy does not establish the claimed combination of local enhancers and distant regions as controls of early limb-bud expression. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

In cavefish eye development, apoptotic degeneration of lens and retina occurs.

“But then many things go wrong in eye development including apoptotic degeneration of lens and retina.”

• cites Jeffery, 2009 sourceSupported

Inserting the bat prx1 limb enhancer into the mouse gene caused recipient mouse forelimbs to develop with relatively longer dimensions.

“The (indirect) causality of this change was then demonstrated by inserting the bat prx1 limb enhancer into the mouse gene, with the result that the forelimbs of the recipient mouse now develop with relatively longer dimensions.”

• cites Cretekos et al., 2008 sourceSupported

Two pigmentation phenotypes in cave Astyanax are due to mutations in protein coding sequences of oca2 and mc1r.

“Two pigmentation phenotypes have been shown to be due to mutations in the protein coding sequences of receptors directly involved in pigmentation, oca2 (Protas et al., 2006) and mc1r (Gross et al., 2009).”

• cites Protas et al., 2006 sourceNot checked — no full text of the source
• cites Gross et al., 2009 sourceSupported

Ectopic spatial expression of shh from the medial interocular region across the ocular fields in cave fish is a cause of eye degeneration.

“A cause is ectopic spatial expression of shh from the normal medial interocular region across the top of the ocular fields in cave fish.”

• cites Jeffery, 2009 sourceSupported
• cites Yamamoto et al., 2004 sourceNot checked — no full text of the source

Cis-regulatory changes affecting yellow and ebony expression account for pigmentation pattern variation in Drosophila.

“Such processes account for variation in pigmentation patterns due to regulatory changes affecting expression of the yellow differentiation gene (Gompel et al., 2005; Rokas and Carroll, 2006); and the ebony differentiation gene (Rebeiz et al., 2009).”

• cites Gompel et al., 2005 sourceNot checked — no full text of the source
• cites Rokas and Carroll, 2006 sourceCould not verify

  Rokas and Carroll is cited alongside Gompel et al. for the yellow-gene portion of the sentence; the ebony portion has a separate citation. Our copy’s “Why Hundreds of Genes Might Not Suffice” section discusses phylogenetic characters and molecular evolution, not regulatory changes affecting yellow expression or Drosophila pigmentation. Searches for yellow, ebony, cis-regulatory changes, and pigmentation found no passage addressing the attributed point; the passages have no page numbers. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites Rebeiz et al., 2009 sourceSupported

The longer relative forearm skeleton length in bats compared to rodents is associated with up-regulation of prx1 after early limb bud stage.

“A candidate regulatory gene known to affect limb skeletal elongation is prx1 (mhox), and in bats this gene is up-regulated after the early limb bud stage compared to mice (Cretekos et al., 2008).”

• cites Cretekos et al., 2008 sourceSupported

A 3' regulatory region causes progressive expression of first anterior then middle hox genes in the limb bud region that will give rise to the forearm.

“One of these operates from the 3' (anterior) end of the cluster and causes the progressive expression of first anterior and then middle hox genes in the limb bud region that will give rise to the forearm.”

• cites Herault et al., 1999 sourcePartly supported

  The Introduction (page unavailable) describes early colinear activation, with Hoxd9 expressed before Hoxd10, and identifies a presumptive forearm expression domain. The reporter results (Fig. 2 section, page unavailable) associate more 3′ positions with forearm expression. But the Discussion says evidence for a separate forearm regulatory element is less compelling and offers alternative explanations, so the claim overstates a 3′ region as the established cause of that progression. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Herault et al., 1998 sourceNot checked — no full text of the source
• cites Kmita et al., 2000 sourceCould not verify

  The ‘Hoxb1 in digits and genitalia’ section discusses a remote regulatory sequence acting on Hox genes in limbs, but its reported expression is posterior, in developing digits. The Discussion mentions sequential Hox activation without placing it in the forearm. Searches for a 3′ regulatory region progressively activating anterior and then middle Hox genes in the future forearm found no passage addressing that claim. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

Shared body plan characters of given clades imply conserved developmental regulatory circuitry.

“Shared body plan characters of given clades ultimately imply conserved developmental regulatory circuitry (Davidson and Erwin, 2009).”

• cites Davidson and Erwin, 2009 sourceSupported

Individual hox genes sometimes act by participating in patterning GRNs, for example in early hindbrain specification, a Box I function.

“Sometimes individual hox genes act by participating, like any other regulatory genes in patterning GRNs, for example in early hindbrain specification, a Box I function.”

• cites Tumpel et al., 2007 sourceSupported
• cites Tumpel et al., 2009 sourceNot checked — no full text of the source

In immune cells, a variety of effector genes is controlled by the same familiar sets of regulatory genes across diverse strategies.

“Immune cells provide the most evidence, for as knowledge of the diverse strategies for immune response, both adaptive and non-adaptive, extends beyond mammals, an amazing variety of effector genes is revealed but the same familiar sets of regulatory genes are found to control their expression.”

• cites Guo et al., 2009 sourcePartly supported

  The ‘Distinctive gene expression profiles’ section reports that lamprey lymphocytes express transcription factors also associated with T cells in jawed vertebrates, alongside cytokines and other immune genes (page not provided). This supports a narrower claim about shared regulatory genes across two adaptive immune systems. It does not establish that those genes control the effector genes’ expression or extend the finding to non-adaptive immune strategies. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Hoffmann, 2003 sourceNot checked — no full text of the source
• cites Hibino et al., 2006 sourceNot checked — no full text of the source

Some differentiation gene batteries are probably among the oldest features of modern developmental GRNs.

“Because of their very widespread distribution, some differentiation gene batteries are probably among the oldest features of modern developmental GRNs (Davidson, 2006; Davidson and Erwin, 2009).”

• cites Davidson, 2006 sourceNot checked — no full text of the source
• cites Davidson and Erwin, 2009 sourceSupported

The GCR is responsible for graded expression of the five posterior hox genes across the A/P dimension of the autopod.

“This “global control region” (GCR) is responsible for a graded expression of the five posterior hox genes across the A/P dimension of the autopod.”

• cites Tarchini and Duboule, 2006 sourcePartly supported

  The ‘Two Waves of Hoxd Gene Expression’ section says the GCR drives expression of five contiguous genes in the presumptive digit domain, which becomes the autopod. The Introduction attributes their anterior–posterior expression asymmetry to the posterior location of Shh signaling; its description of a progressive decrease concerns transcriptional efficiency across the genes, not a GCR-driven gradient across the autopod. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Ocular photoreceptor cells are a pan-bilaterian cell type in which the Box IV GRN controlling receptor subtypes operates downstream of K50 homeodomain family regulatory genes.

“Ocular photoreceptor cells provide another example of a pan-bilaterian cell type in which the Box IV GRN controlling the various subtypes of receptors (rhabdomeric receptors in insects, and rods and cones in vertebrates) operate downstream of regulatory genes of the K50 homeodomain family (Mishra et al., 2010; Ranade et al., 2008).”

• cites Mishra et al., 2010 sourcePartly supported

  The Introduction (p. 2) identifies Otd as a K50-family factor and draws a parallel with vertebrate Crx. The Results (pp. 6–7) show that Otd regulates some Drosophila rhodopsins, but others depend on Pph13, a Q50 factor. The paper does not establish that a Box IV network controlling receptor subtypes operates downstream of K50 genes across bilaterians. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Ranade et al., 2008 sourcePartly supported

  The Direct and indirect targets of Otd section identifies Otd/OTX/CRX as K50-type homeodomain proteins, and the Conclusions describe their regulation of photoreceptor genes in flies and mice. But the Conclusions say the two lineages use substantially different genetic cascades and present an ancestral regulatory relationship as a hypothesis; the paper does not establish a conserved Box IV network controlling all the receptor subtypes named in the claim. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Anterior group hoxa and hoxb genes, together with krox and Kreisler, establish recursively wired, extremely conserved, rhombomere-specific GRNs.

“Together with other important regulatory genes such as krox and Kreisler, the anterior group hoxa and hoxb genes establish recursively wired, extremely conserved, rhombomere specific GRNs (Tumpel et al., 2007; 2009).”

• cites Tumpel et al., 2007 sourcePartly supported

  The section “A model for the gene regulatory network specifying r4 identity” (page unavailable) describes a rhombomere-4 Hox network with highly conserved auto- and cross-regulatory mechanisms. The paper also discusses Krox20-dependent regulation in rhombomeres 3 and 5, but the passages do not establish the broader claim that anterior hoxa and hoxb genes together with Krox and Kreisler form extremely conserved, rhombomere-specific networks; a search for Kreisler found no relevant passage. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Tumpel et al., 2009 sourceNot checked — no full text of the source

A relatively recent co-option of an entire body part has occurred in teleost fish, resulting in the formation of a secondary jaw in the same location where ancient pharyngeal teeth developed.

“A relatively recent co-option of an entire body part has occurred in teleost fish, resulting in the formation of a secondary jaw in the same location where ancient pharyngeal teeth developed (Fraser et al., 2009).”

• cites Fraser et al., 2009 sourcePartly supported

  The Discussion, under “The Origin of an Ancient Dental Network and Deployment on Old and New Jaws” (page unavailable), says that a recent adaptation of the pharyngeal skeleton in some advanced teleosts led to a new toothed jaw where the ancient pharyngeal dental network was located. It does not describe this as the co-option of an entire body part; the co-opted element is the dental gene network. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Regulatory genes exclusive to the embryonic GRN determine the embryonic location in which the skeletogenic GRN is activated.

“Regulatory genes exclusive to the embryonic GRN are those determining the embryonic location in which the skeletogenic GRN is activated.”

• cites Gao and Davidson, 2008 sourcePartly supported

  The Results and Discussion identify a micromere-specific specification system that establishes the embryonic regulatory state into which the shared skeletogenic apparatus is linked. But the Discussion also identifies genes used in embryonic micromeres and not juvenile skeletogenic centers—including foxB, foxO, tel, and tbr—as parts of the skeletogenic apparatus or possible cell-biology controls. Thus, the paper does not support saying that all regulatory genes exclusive to the embryonic GRN determine its location of activation. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

A comparison between sea urchin and sea star endomesodermal GRNs revealed an extremely conserved 5-gene subcircuit surrounded by linkages none of which had survived the half billion years since divergence without change.

“Sometimes the contrast between the conserved and non-conserved parts of a given GRN is quite dramatic, as in a comparison between sea urchin and sea star endomesodermal GRNs that revealed an extremely conserved, 5-gene subcircuit, surrounded by linkages not one of which had survived the half billion years since divergence without change (Hinman and Davidson, 2007).”

• cites Hinman and Davidson, 2007 sourcePartly supported

  The introduction describes a conserved five-gene subcircuit in sea star and sea urchin GRNs and dates their common ancestor to about 500 million years ago. The Discussion reports extensive rewiring outside the subcircuit, but the Results explicitly identify a conserved Delta-to-gatae regulatory linkage. Thus, the claim that not one surrounding linkage survived unchanged is too absolute. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

In sea urchins, a Class-specific evolutionary modification caused the acquisition of an embryonic skeleton not present in other echinoderms.

“One example of a subcircuit-level co-option event has been discovered in sea urchins, in which a Class-specific evolutionary modification has caused the acquisition of an embryonic skeleton not present in other echinoderms.”

• cites Gao and Davidson, 2008 sourcePartly supported

  The Discussion (Heterochrony; page unavailable) describes an evolutionary transfer of a skeletogenic gene-regulatory subnetwork to an embryonic developmental address in sea urchins. But the paper’s introductory passage says that ophiouroid embryos also have skeletons, built differently. The modification is therefore supported; the claim that an embryonic skeleton is absent from all other echinoderms is not. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Oliveri et al., 2008 sourcePartly supported

  The paper describes the skeletogenic micromere lineage in modern sea urchins (Introduction, p. 1), and the Results (p. 2) show a late gastrula with a forming skeleton. It does not establish that a class-specific evolutionary modification or subcircuit co-option caused the skeleton’s acquisition, or compare its presence with other echinoderms. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Every major aspect of A/P patterning analyzed at the gene interaction level appears to include some different linkages in Drosophila compared to Tribolium.

“Every major aspect of A/P patterning analyzed at the gene interaction level appears to include some different linkages in Drosophila compared to Tribolium.”

• cites Kotkamp et al., 2010 sourceNot checked — no full text of the source
• cites Choe et al., 2006 sourcePartly supported

  The Discussion (page not provided) identifies different pair-rule gene interactions in Drosophila and Tribolium, including opposite regulatory relationships involving eve and odd. The paper analyzes pair-rule patterning, not every major aspect of anterior–posterior patterning at the gene-interaction level, so the claim extends beyond its findings. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Marques-Souza et al., 2008 sourcePartly supported

  The paper identifies differences in specific gene interactions: the Regulation between gap genes section (p. 6) says a hunchback–giant interaction seen in Drosophila is not conserved, and The role of hunchback in segmentation (p. 7) describes a possible difference in gap-gene–pair-rule coupling. It does not establish that every major aspect of A/P patterning has different linkages; The conserved core elements of hunchback function (p. 7) also identifies interactions shared by the two insects. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

To make sense of the physical mechanisms that underlie the origin of animal body plans and their innovative diversification during and since the Cambrian, we must consider how change in DNA sequence can affect development of the body plan at the system level.

“To make sense of the physical mechanisms that underlie the origin of animal body plans (Davidson and Erwin, 2009), and during and since the Cambrian their innovative diversification, we must consider how change in DNA sequence can affect development of the body plan at the system level.”

• cites Davidson and Erwin, 2009 sourceSupported

In Tribolium there is a possibly pleisiomorphic kernel-like segmentation subcircuit consisting of mutual interconnections among eve, runt, and odd, which runs sequentially to pattern the forming segments.

“and upstream of this, in Tribolium is a possibly pleisiomorphic kernel-like segmentation subcircuit, consisting of mutual interconnections among eve, runt, and odd, which runs sequentially to pattern the forming segments (Choe et al., 2006).”

• cites Choe et al., 2006 sourcePartly supported

  The Discussion describes a circuit in which Tc-eve activates Tc-run, Tc-run activates Tc-odd, and Tc-odd represses Tc-eve; one cycle prepatterns a two-segment unit. The paper calls this a core mechanism and suggests it may apply to other arthropods, but does not establish or propose that the circuit is plesiomorphic. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Independent populations of two different genera of stickleback fish repeatedly lost external pelvic spines during the last 10,000-20,000 years.

“during the last 10,000–20,000 years independent populations of two different genera of these fish have repeatedly lost external pelvic spines.”

• cites Shapiro et al., 2006 sourceNot checked — no full text of the source

pitx1 is involved in pattern formation upstream of pelvic girdle specification.

“The pitx1 gene is clearly involved in pattern formation functions upstream of pelvic girdle specification”

• cites Cole et al., 2003 sourceNot checked — no full text of the source
• cites Shapiro et al., 2006 sourceNot checked — no full text of the source

In spineless stickleback, pitx1 is not expressed in pelvic buds even though its coding region is intact.

“in spineless fish there is no pitx1 expression in the pelvic buds even though the coding region of the gene is intact (Cole et al., 2003; Shapiro et al., 2006).”

• cites Cole et al., 2003 sourceNot checked — no full text of the source
• cites Shapiro et al., 2006 sourceNot checked — no full text of the source

A recurrent change in cave Astyanax is degeneration of eyes during larval development.

“A recurrent change in cave Astyanax is degeneration of eyes during larval development.”

• cites Jeffery, 2005, 2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Diverse stickleback isolates bear the same or overlapping genetic lesions, even in crosses between species from different genera with the same spine reduction phenotype.

“Genetic complementation tests show that diverse isolates bear the same or overlapping genetic lesions, and this is so even in crosses of species from different genera displaying the same spine reduction phenotype.”

• cites Shapiro et al., 2006 sourceNot checked — no full text of the source

Inductive signaling interactions do show a higher rate of evolutionary change.

“Indeed they do, as discussed elsewhere (Davidson and Erwin, 2006; Erwin and Davidson, 2009).”

• cites Davidson and Erwin, 2006 sourceNot checked — no full text of the source
• cites Erwin and Davidson, 2009 sourceNot checked — no full text of the source

Cis-regulatory evolution in shavenbaby determines its expression and minute trichome distribution differences among Drosophila species.

“cis-regulatory evolution in the shavenbaby (ovo) regulatory gene, which controls trichome differentiation and morphogenesis, determines where this gene is expressed, and thereby the minute pattern differences in trichome distribution distinguishing Drosophila species (McGregor et al., 2007).”

• cites McGregor et al., 2007 sourceNot checked — no full text of the source

Studies of direct hox gene targets reveal other regulatory genes and far downstream genes encoding proteins active in apoptosis, cell cycle control, cell adhesion, cell polarity, non-canonical signalling, and cytoskeletal functions.

“Studies of direct hox gene targets reveal both other regulatory genes and far downstream genes encoding proteins active, e.g., in apoptosis, cell cycle control, cell adhesion, cell polarity, non-canonical signalling, and cytoskeletal functions (Cobb and Duboule, 2005; Hueber and Lohmann, 2008; Pearson et al., 2005).”

• cites Cobb and Duboule, 2005 sourceNot checked — no full text of the source
• cites Hueber and Lohmann, 2008 sourceNot checked — no full text of the source
• cites Pearson et al., 2005 sourceNot checked — no full text of the source

Many well-characterized cis-regulatory modules controlling specific spatial and temporal aspects of anterior hox gene expression are known in mammals and are often conserved to fish.

“many very well characterized cis-regulatory modules controlling very specific spatial and temporal aspects of anterior hox gene expression are known in mammals, and often conserved to fish (Tumpel et al., 2009).”

• cites Tumpel et al., 2009 sourceNot checked — no full text of the source

In Drosophila, many cis-regulatory modules control each aspect of expression of each hox gene.

“In Drosophila a plethora of cis-regulatory modules control each aspect of expression of each gene.”

• cites Ho et al., 2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Maeda and Karch, 2009 sourceNot checked — no full text of the source
• cites Simon et al., 1990 sourceNot checked — no full text of the source

The causal developmental mechanism for diverse beak morphologies in Galapagos finches involves BMP4 and Ca++ signaling.

“The causal developmental mechanism underlying the adaptively diverse beak morphologies of Darwin’s classic series of Galapagos finch species was solved in these terms by Abzanov et al. (2006, 2004).”

• cites Abzanov et al. (2006, 2004)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Hox genes are not required for embryonic development of organisms that use fixed cell lineages for specification, such as C. elegans, sea urchins, and Ciona.

“hox genes are not required for embryonic development of organisms that utilize fixed cell lineages for specification (Davidson, 1990), e.g., in C. elegans which lacks both a coherent hox complex and many hox genes (Aboobaker and Blaxter, 2010); in sea urchins (Martinez et al., 1999); or in Ciona, which also lacks a coherent hox complex (Ikuta et al., 2010).”

• cites Davidson, 1990 sourceNot checked — no full text of the source
• cites Aboobaker and Blaxter, 2010 sourceNot checked — no full text of the source
• cites Martinez et al., 1999 sourceNot checked — no full text of the source

In stickleback fishes with loss of pigmentation in lacustrine forms, cis-regulatory changes rather than coding region mutations are responsible.

“in stickleback fishes where there is also loss of pigmentation in lacustrine forms, cis-regulatory changes rather than coding region mutations are responsible (Miller et al., 2007).”

• cites Miller et al., 2007 sourceNot checked — no full text of the source

During cavefish embryogenesis, eyes initially develop similarly to surface conspecifics, including expression of many regulatory genes.

“During embryogenesis of cavefish, the eyes initially develop similarly to those of surface conspecifics, including expression of many regulatory genes (Jeffery, 2005, 2009).”

• cites Jeffery, 2005, 2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

hox6PG genes promote rib formation.

“On the other hand hox6PG genes promote rib formation.”

The axial skeleton in vertebrates varies greatly in distribution of vertebral morphologies, a developmental function of hox gene expression patterns.

“Another example concerns the axial skeleton in vertebrates, which vary greatly in the distribution of vertebral morphologies, again a developmental function of hox gene expression patterns.”

Specific sets of vertebrae require hox5PG, hox6PG, hox9PG, hox10PG, and hox11PG.

“It is now possible to state just which sets of vertebrae require hox5PG, hox6PG, hox9PG, hox10PG, and hox11PG (for review, Wellik, 2009).”

• cites Wellik, 2009 sourceNot checked — no full text of the source

Early expression of 5' hox genes at the posterior margin of the limb bud causes shh expression in these cells, setting up anterior and posterior regulatory states in the limb bud.

“The early expression of 5' hox genes at the posterior margin of the bud causes expression of the shh gene in these cells, ultimately setting up anterior and posterior regulatory states in the limb bud (Zakany et al., 2004).”

• cites Zakany et al., 2004 sourceNot checked — no full text of the source

During the autopod expression phase, the GCR responds to graded Shh levels, contributing to the nested pattern of hox gene expression in the autopod.

“Later, during the autopod expression phase, the GCR responds in turn to graded levels of Shh contributing to the nested pattern of hox gene expression in the autopod”

Cis-regulatory sequences combinatorially determine which regulatory inputs affect a gene's expression and which other genes it affects, thereby hardwiring functional linkages among regulatory genes into network subcircuits.

“The cis-regulatory sequences combinatorially determine which regulatory inputs will affect the expression of each gene and what other genes it will affect; that is, they hardwire the functional linkages among the regulatory genes, forming network subcircuits.”

• AssumptionRests on an assumption: The genomic control apparatus for a developmental episode consists of specifically expressed transcription factor genes and their cis-regulatory regions.

Morphological differences within body parts are more likely caused by differences in the spatial assignment of cell fate domains determined by body part patterning GRNs of Box III.

“Morphological differences within body parts are more likely to be caused by differences in the spatial assignment of cell fate domains determined by the body part patterning GRNs of Box III.”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

The phenotypic functionality of a co-optive change in regulatory gene expression does not depend on homozygosity.

“But in fact phenotypic functionality of a co-optive change in regulatory gene expression will not depend on homozygosity.”

• cites Ruvkun et al. (1991)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Davidson and Erwin (2010) sourceNot checked — no full text of the source

Differences in the relative positions of body parts can arise even when embryonic patterning GRNs and body part specification GRNs are conserved, by rewiring the connections between these functions.

“Differences in the position of body parts relative to each other, which basically insert body parts of different identities at given locations could occur even when embryonic patterning GRN and body part specification GRNs are conserved, simply by rewiring the connections between these functions”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

A relevant change in gene regulatory network structure produces a derived change in network operation relative to the immediately ancestral networks.

“The result of relevant change in GRN structure is derived change in GRN operation, compared to the immediately ancestral GRNs.”

Inductive signaling interactions are likely to show a higher rate of evolutionary change.

“In organisms of different spatial geometry, inductive signaling relationships will differ, and thus, inductive signaling interactions are likely to show a higher rate of evolutionary change.”

There is an intrinsically high possibility of evolutionary reorganization of gene regulatory network structure by cis-regulatory gain-of-function co-options, given the rapidity of cis-regulatory evolution and the haplo-dominance of such changes.

“There is an intrinsically high possibility of evolutionary re-organization of GRN structure by cis-regulatory gain of function co-options, given the general rapidity of cis-regulatory evolution, and the haplo-dominance of gain of function changes in regulatory gene expression.”

pitx1 functions in a Box III body part-specific patterning GRN in stickleback fish.

“its expression prior to the terminal phases of pelvic skeletogenesis indicates that it also functions in a Box III body part-specific patterning GRN in stickleback fish.”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

Gain-of-function cis-regulatory co-options that produce regulatory gene expression in new domains act dominantly.

“As initially pointed out by Ruvkun et al. (1991) and further discussed by Davidson and Erwin (2010), gain of function cis-regulatory co-options that produce regulatory gene expression in new domains act dominantly, and this has fundamental consequences for evolutionary process.”

• cites Ruvkun et al. (1991)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Davidson and Erwin (2010) sourceNot checked — no full text of the source

The consequences of any given cis-regulatory mutation depend entirely on where in the gene regulatory network hierarchy the affected node lies.

“The consequences of any given cis-regulatory mutation will depend entirely on where in the GRN hierarchy the affected cis-regulatory node lies.”

For internal changes, loss or gain of a target site can cause either loss or gain of function, depending on whether the bound factor is an activator or repressor.

“Of the internal changes in Table 1, note that loss or gain of a given target site might each cause either loss or gain of function, depending on whether the factor binding the site is an activator or repressor.”

Development proceeds through phases, reflecting the sequential hierarchy of the gene regulatory network control system.

“Development progresses from phase to phase and this fundamental phenomenon reflects the underlying sequential hierarchy of the GRN control system.”

Only intra-modular cis-regulatory changes that produce qualitative gain or loss of target sites can co-opt a network node to a new temporal/spatial expression domain and thereby alter functional network topology.

“As Table1 indicates, only those intra-modular cis-regulatory sequence changes which produce qualitative gain or loss of target sites can result in the co-option of the respective network node to a new temporal/spatial expression domain and thus in the alteration of functional GRN topology.”

Phylum-level morphological differences are expected to arise in the gene regulatory networks underlying Boxes I and II.

“Phylum-level morphological differences are therefore expected to occur in the GRNs underlying Boxes I and II.”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

Rapidly evolving, reduced, or regressive phenotypes can be due to gain of function as well as loss of function mutations.

“rapidly evolving, reduced, or regressive phenotypes can be due to gain of function as well as loss of function mutations.”

Changing the functional organization of gene regulatory networks that control body plan development is a cause of evolutionary change in animal morphology.

“Alteration of the functional organization of the gene regulatory networks (GRNs) that control development of the body plan causes evolutionary change in animal morphology.”

• AssumptionRests on an assumption: The body plan of each animal species is formed by an inherited genomic regulatory program for embryonic development.

There are points of flexibility in developmental GRNs where co-optive gain or loss of function regulatory changes may have large effects.

“there are points of “flexibility” in developmental GRNs, where co-optive gain of function, or loss of function, regulatory changes may have large effects.”

Most changes in gene regulatory network structure are rooted in cis-regulatory alterations, both in principle and in fact.

“Most changes in GRN structure are rooted in cis-regulatory alterations, both in principle and in fact, a fundamental theme of the following review.”

Because gene regulatory network topology is encoded directly in cis-regulatory sequence at its nodes, evolutionary changes in that sequence have great potency to alter developmental network structure and function.

“Because GRN topology is encoded directly in cis-regulatory sequence at its nodes, evolutionary changes in this sequence have great potency to alter developmental GRN structure and function.”

The mosaic view of gene regulatory network evolution accounts for major evolutionary patterns, including hierarchical phylogeny and discontinuities of paleontological change and stasis.

“This mosaic view of the evolution of GRN structure explains major aspects of evolutionary process, such as hierarchical phylogeny and discontinuities of paleontological change and stasis.”

Many internal cis-regulatory sequence changes produce only quantitative effects, provided the qualitatively complete set of interactions is assured by target site identity.

“Many internal cis-regulatory sequence changes will produce quantitative effects only, so long as the qualitatively complete set of interactions is assured by the identity of the target sites.”

Evolution of novel developmental GRN features must proceed to some extent by combining, recombining, activating and inactivating diverse subcircuits in given spatial domains of the embryo.

“Evolution of novel developmental GRN features must thus proceed to some extent as a process in which diverse subcircuits are combined, recombined, activated and inactivated in given spatial domains of the embryo.”

Contextual cis-regulatory changes of several kinds may be a major source of evolutionary gene regulatory network re-design.

“An important implication of Table 1 is that contextual (external) cis-regulatory changes of several kinds may be a major source of evolutionary GRN re-design.”

A primary way that gene regulatory network structure evolves is through changes in cis-regulatory modules that set regulatory gene expression.

“A major mechanism of evolutionary change in GRN structure is alteration of cis-regulatory modules that determine regulatory gene expression.”

• AssumptionRests on an assumption: The genomic control apparatus for a developmental episode consists of specifically expressed transcription factor genes and their cis-regulatory regions.

Physical and functional modularity in the control systems of regulatory genes is among the fundamental characteristics of animal genomes that permit and produce evolution of development by GRN reorganization.

“Physical and functional modularity in the control systems of regulatory genes is thus among the fundamental characteristics of animal genomes that permit, and indeed, that produce, evolution of development by GRN reorganization.”

Underlying evolutionary change in body part development often involves alterations in deployment of signal systems via cis-regulatory apparatus controlling time and place of inductive signaling.

“The results have thus far often resolved into demonstration of alterations in the deployment of signal systems in the development of these parts; i.e., the underlying evolutionary change is in the cis-regulatory apparatus controlling time and place of inductive signaling, just as predicted earlier.”

GRN evolution by regulatory gain and loss of function of expression of these genes would be impossible if these control systems were not generally modular.

“GRN evolution by regulatory gain and loss of function of expression of these genes would be utterly impossible were these control systems not in general modular”

• AssumptionRests on an assumption: Almost all regulatory and signaling genes function in multiple time-space compartments and multiple GRNs during development.

The simplest cases of evolutionary trait loss are deleterious mutations in far downstream differentiation genes.

“The simplest cases of evolutionary trait loss are deleterious mutations in far downstream differentiation genes.”

These examples imply the existence of Box III GRN subcircuits in which the targeted genes participate.

“these examples differ from the foregoing in that they imply the existence of Box III GRN subcircuits in which the targeted genes participate.”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

These Drosophila studies provide examples of cis-regulatory site addition and quantitative or qualitative gain and loss of function due to internal DNA sequence change.

“These studies afford multiple real examples of cis-regulatory site addition, and quantitative as well as qualitative cis-regulatory gain and loss of function due to internal DNA sequence change (cf. Table1).”

In organisms with coherent hox complexes, hox genes are expressed in a vectorial or sequential fashion with respect to body plan or body part coordinates.

“in organisms in which coherent hox complexes exist they are expressed in a vectorial or sequential fashion with respect to the coordinates of the body plan or the body part”

The prevalence of local cis-regulatory hox gene control modules explains how hox genes can function in animals lacking large hox gene clusters.

“The prevalence of local cis-regulatory hox gene control modules explains how these genes can function in animals which lack large hox gene clusters.”

Mechanistic studies of intra- and inter-specific evolutionary variation illuminate evolutionary changes in Box III-type pattern formation GRNs that determine morphological characteristics of body parts.

“Mechanistic studies of intra- and inter-specific evolutionary variation illuminate the next level up as well, that is, evolutionary changes (other than simple loss of function) in the Box III-type pattern formation GRNs that determine the morphological characteristics of given body parts.”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

The modularity generally typical of cis-regulatory systems controlling expression of regulatory and signaling genes in animal genomes has a powerful evolutionary explanation.

“we see a powerful evolutionary explanation for the modularity generally typical of the cis-regulatory systems controlling expression of regulatory and signaling genes in animal genomes”

• cites Davidson, 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Davidson, 2006 sourceNot checked — no full text of the source

In peripheral gene examples, the phenotype is wholly encompassed by changes in a single cis-regulatory system.

“in the peripheral gene examples above, the phenotype is wholly encompassed by changes in a single cis-regulatory system.”

Hox genes work at diverse levels, so their functions cannot be simply interpreted in terms of developmental GRN structure.

“The variety of effects precludes any simple interpretation of the functions of these genes in the terms of developmental GRN structure, for the simple reason that they work at diverse levels.”

Each specific hox gene enhancer responds to local upstream regulatory states produced by earlier developmental GRNs.

“Each specific hox gene enhancer responds to local upstream regulatory states which are the product of earlier developmental GRNs, just as in any other developmental process.”

Loss of function in a single cis-regulatory module has specific effects that under certain conditions are adaptive.

“Loss of function in a single cis-regulatory module, on the other hand, has specific effects that under certain conditions are adaptive.”

In cave Astyanax, regulatory changes have caused a spatial gain of function in shh transcription resulting in eye regression.

“Though yet undefined at the sequence level, in cave Astyanax regulatory changes have evidently caused a spatial gain of function in shh transcription resulting in regression of the eyes.”

Distinct mechanisms account for the locations in the body plan where individual hox genes are expressed.

“The genomic organization of hox gene clusters indicates that distinct mechanisms account for the locations in the body plan where individual hox genes are expressed in development.”

Hox genes provide negative or positive cis-regulatory inputs into genes engaged in GRN circuits that do spatial patterning and body part morphogenesis.

“So in summary, the common statement that hox genes “pattern” this or that body part means that they provide negative or positive cis-regulatory inputs into genes which are engaged in the GRN circuits which actually do the work of spatial patterning and body part morphogenesis.”

Hox genes more often operate in an evolutionarily flexible way, with changes in their functions directly correlated with evolutionary change in positioning and organization of body parts.

“But more often they operate in another, evolutionarily flexible way, such that change in their functions has been directly correlated, in many comparative observations, with evolutionary change in both the positioning and organization of body parts.”

Since the regulatory landscape to which local hox enhancers respond can differ greatly between organisms, local enhancers must have evolved in clade-specific ways.

“since the regulatory landscape to which the local enhancers must respond can be very different in different organisms, they themselves must have evolved in clade specific ways.”

• AssumptionRests on an assumption: The regulatory landscape to which local hox enhancers respond can differ greatly between organisms.

These features, and developmental canalization due to the upstream position of such kernels in the body part GRN, explain their exceptional evolutionary conservation.

“These features, and developmental canalization due to the upstream position of such kernels in the body part GRN, explain their exceptional evolutionary conservation.”

In cases where final structures are diverse and develop via diverse pattern formation and morphogenetic mechanisms, only the Box II GRN circuits encoding initial establishment of the progenitor field plus final deployment of conserved cell types may be conserved.

“However, in cases where the final structures are diverse, and develop via very diverse pattern formation and morphogenetic mechanisms, it may be that only the Box II GRN circuits encoding the initial establishment of the progenitor field from which the body part will be built are conserved, plus the final deployment of conserved cell types.”

Comparative GRN analysis is beginning to reveal kernels in which regulatory genes wired together in certain conserved linkages execute upstream regulatory functions in development of given body parts.

“Comparative GRN analysis is beginning to reveal “kernels” (Davidson and Erwin, 2006), in which regulatory genes wired together in certain conserved linkages execute upstream regulatory functions in development of given body parts.”

• cites Davidson and Erwin, 2006 sourceNot checked — no full text of the source

In these cell types both downstream effector genes and their immediate regulatory apparatus are deployed in a manner that is widely conserved.

“That is, in these cell types both downstream effector genes and their immediate regulatory apparatus are deployed in a manner that is widely conserved.”

Hox genes act as regionally active switches sitting outside the boxes containing morphogenetic patterning GRNs.

“these hox genes act as regionally active switches that we can imaging sitting on the outside of the boxes containing the morphogenetic patterning GRNs.”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

There is a pattern of conservation in pan-bilaterian cell types in which downstream effector genes are clade specific while the definitive upstream regulatory states are conserved across clades.

“But there is another, profoundly interesting pattern of conservation displayed by pan-bilaterian cell types, in which the downstream effector genes are clade specific, while the definitive upstream regulatory states are conserved across clades.”

Evolutionary rewiring of GRN architecture by cis-regulatory co-optive change of given linkages among regulatory genes is the most common upper level evolutionary mechanism by which developmental process is altered.

“Evolutionary rewiring of GRN architecture by means of cis-regulatory co-optive change of given linkages among regulatory genes is the most common upper level evolutionary mechanism by which developmental process is altered.”

Gene expression data by themselves are a poor index of evolutionary conservation.

“Thus gene expression data by themselves are a poor index of evolutionary conservation.”

The deployment of hox switches and linkages between them and body part-specific subcircuits are more flexible in evolution than the internal structure of those subcircuits.

“In evolution the deployment of these switches, and the linkages between them and the body part specific subcircuits, are far more flexible than is the internal structure of these subcircuits.”

During evolution the identity of effector genes can change radically while the biological function of the cell type remains the same.

“During evolution the identity of the effector genes can change radically, whereas the biological function of the cell type remains the same”

The evolution of diverse animal body plans requires large-scale processes of change in ancestral developmental GRN architecture.

“Unless all forms were “sprung forth fully blown” like Athena from the head of Zeus, the evolution of the diverse body plans of animals requires large scale processes of change in ancestral developmental GRN architecture.”

Developmental gene use cannot be regarded as conserved unless the regulatory linkages surrounding the genes in the GRN are conserved.

“Developmental gene use cannot truly be regarded as conserved unless the regulatory linkages surrounding the genes in the GRN are conserved.”

Development of the limb depends directly on deployment of hox gene expression at several levels of the underlying GRN.

“Development of the limb depends directly on deployment of hox gene expression at several levels of the underlying GRN.”

Where vectorial inputs are required, hox genes intervene in local, mid-development patterning functions (Box III).

“Where vectorial inputs are required, hox genes intervene in local, mid-development, patterning functions (Box III).”

• AssumptionRests on an assumption: The Box I/II/III hierarchical classification of developmental GRNs is a valid framework for predicting where evolutionary changes occur.

Development of the body plan is a heritable regulatory system process, which can be represented and comprehended only in terms of genomically encoded GRN architecture.

“For development of the body plan is a heritable regulatory system process, which we can represent and manipulate and comprehend only in terms of genomically encoded GRN architecture.”

One substantial difference exists: expression of a set of hox genes in the pharyngeal but not the oral jaw.

“However, one substantial difference exists, which is the expression of a set of hox genes in the pharyngeal but not the oral jaw.”

If the same was true in the teleost ancestor, a prerequisite for the evolutionary co-option of the jaw GRN to a caudal pharyngeal arch in Cichlids would have been the uncoupling of this developmental program from the repressive hox input.

“Therefore, if the same was true in the teleost ancestor, a prerequisite for the evolutionary co-option of the jaw GRN to a causal pharyngeal arch in Cichlids would have been the uncoupling of this developmental program from the the repressive hox input.”

The theory of evolution by change in GRN architecture generates the path to experimental validation of evolutionary process by synthetic changes in developmental GRNs.

“The theory of evolution by change in GRN architecture also generates the path to experimental validation of evolutionary process by synthetic changes in developmental GRNs.”

Since the short germ band mode of development appears to be pleisiomorphic for insects and their sister group the crustaceans, the linkages seen in the early A/P patterning GRN of Tribolium may be closer to the ancestral linkages than the derived linkages of Drosophila GRNs.

“Since the short germ band mode of development appears to be pleisiomorphic for insects and their sister group the crustaceans, the linkages seen in the early A/P patterning GRN of Tribolium, for example, may be closer to the ancestral linkages than the derived linkages of Drosophila GRNs.”

The GRN of a common ancestor is the source structure for diverse alterations in that structure in the derived descendants.

“That is, the GRN of a common ancestor is the source structure for diverse alterations in that structure in the derived descendants.”

The same sequence of regulatory gene expressions is observed also along the anteroposterior axis in the head neuroectoderm of Drosophila and Saccoglossus, a hemichordate lacking appendages.

“Interestingly, this very same sequence of regulatory gene expressions is observed also along the anteroposterior axis in the head neuroectoderm of Drosophila and Saccoglossus, a hemichordate lacking appendages.”

The jaw-forming patterning GRN would be expressed in more posterior pharyngeal arches were it not for the repressive hox gene switch.

“In other words, the jaw-forming patterning GRN would be expressed in more posterior pharyngeal arches were it not for the repressive hox gene switch.”

By modifying probably only a small number of cis-regulatory sequences, the skeletogenic GRN subcircuit was re-deployed such that it is activated both in the embryo and in the adult, most likely by use of the exact same genomic sequences.

“Thus, by modifying probably only a small number of cis-regulatory sequences, the skeletogenic GRN subcircuit was re-deployed such that it is activated both in the embryo and in the adult, most likely by use of the exact same genomic sequences.”

Not all parts of GRN structure are equally accessible to change.

“But of course, not all parts of the structure are equally accessible to change, for the reasons we have tried here to point out.”