Graded dorsal and differential gene regulation in the Drosophila embryo.

High levels of nuclear Dorsal present in ventral regions activate genes such as twist and snail, which are required for specification of the mesoderm.

“High levels of nuclear Dorsal present in ventral regions activate genes such as twist (twi) and snail (sna), which are required for specification of the mesoderm”

• cites Simpson 1983 sourceNot checked — no full text of the source
• cites Thisse et al. 1987 sourcePartly supported

  The Discussion reports that dorsal (dl) activity is required for twist expression in presumptive mesodermal cells, and the introductory passage says twist and snail are involved in dorsoventral development. The paper does not establish that high levels of nuclear Dorsal in ventral regions activate both genes; it tests twist expression, not snail activation. Page numbers are not available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Jiang et al. 1991 sourceSupported

Downstream of Spatzle-mediated activation of Toll, intracellular signaling occurs through maternal factors including Weckle, Myd88, Tube, and Pelle, which function together to facilitate degradation of Cactus, releasing Dorsal from cytoplasmic retention.

“Downstream of the Spz-mediated activation of Toll, intracellular signaling occurs through the action of several maternal factors.These proteins, which include Weckle, Myd88, Tube, and Pelle, function together to facilitate the degradation of Cactus, a cytoplasmic tethering protein, thereby releasing Dorsal from cytoplasmic retention”

• cites Hecht and Anderson 1993 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Belvin et al. 1995 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Grosshans et al. 1999Not matched

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

The reorientation of axes was accomplished through the ectopic expression of an anterior HIGH-posterior LOW gradient of constitutively activated Toll receptor.

“This reorientation of axes was accomplished through the ectopic expression of an anterior HIGH -posterior LOW gradient of constitutively activated Toll receptor.”

• cites Huang et al. 1997 sourceSupported

A genome-wide computational search identified an additional set of sequences, denoted the TAGteam (CAGGTAG and slight variations), which is present in cis-regulatory elements of many genes expressed at the onset of zygotic transcription.

“A genome-wide computational search also identified an additional set of sequences, denoted the “TAGteam” (CAGGTAG and slight variations of this sequence), which is present in cis-regulatory elements of many genes expressed at the onset of zygotic transcription”

• cites ten Bosch et al. 2006 sourceNot checked — no full text of the source
• cites De Renzis et al. 2007 sourcePartly supported

  The Results sections on regulatory motifs and zygotic-genome activation report a computational search that found CAGGTAG and its variants upstream of many early zygotic genes. However, this paper calls the motif the “7mer,” not “TAGteam,” so it does not support the attributed name. The supplied passages have no page numbers. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Classical genetic screens identified 10 genes that function in the early embryo to control dorsoventral patterning: sna, twi, single-minded, m8, brinker, rho, sog, tld, zen, and dpp.

“Classical genetic screens identified 10 genes that function in the early embryo to control DV patterning (sna, twi, single-minded [sim], m8, brinker [brk], rho, sog, tld, zen, and dpp)”

• cites Stathopoulos and Levine, 2004 sourceNot checked — no full text of the source
• cites Klambt et al. 1989 sourceNot checked — no full text of the source
• cites Bier et al. 1990 sourcePartly supported

  The paper’s discussion of dorsoventral patterning in the early embryo identifies twi, sim, zen, dpp, and rho as relevant genes. It does not state that classical screens identified the specified set of 10 genes, and the passages do not support the remaining names in that list. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Classical studies based on the analysis of cis-regulatory sequences showed that Dorsal can function as either an activator or a repressor to control gene expression along the dorsoventral axis.

“First, classical studies based on the analysis of cis-regulatory sequences showed that Dorsal can function as either an activator or a repressor to control gene expression along the DV axis”

• cites Jiang et al. 1993 sourceSupported

Synergistic DNA binding between Dorsal and Twist, a bHLH transcription factor, permits gene expression in more lateral regions of the embryo where neither Dorsal nor Twist is capable of inducing gene expression independently.

“synergistic DNA binding between Dorsal and Twist, a bHLH transcription factor, permits gene expression in more lateral regions of the embryo where neither Dorsal nor Twist is capable of inducing gene expression independently”

• cites Gonzalez-Crespo and Levine 1993 sourcePartly supported

  In “The role of dl-HLH interactions in development” (page unavailable), the paper says Dorsal–Twist interactions have been proposed to let intermediate Dorsal levels in ventrolateral regions activate snail expression; it also describes their effects as multiplicative. In “Mechanism of dl-HLH interactions” (page unavailable), cooperative promoter activation by Dorsal–Twist complexes is presented as a possibility, not an established finding of synergistic DNA binding. The copy does not establish that neither protein could induce expression independently in those regions. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Jiang and Levine 1993 sourcePartly supported

  The Discussion (page unavailable) says efficient Dorsal activation requires synergistic interactions with bHLH proteins. It does not identify Twist as the partner or describe synergistic DNA binding that permits expression in more lateral regions. The Introduction (page unavailable) instead says low levels of Dorsal activate genes such as rhomboid in lateral regions, so it does not support the assertion that Dorsal cannot induce expression there independently. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Stathopoulos and Levine 2002bNot matched

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

The affinity of Dorsal binding sites within cis-regulatory sequences influences the domain of target-gene expression.

“the affinity of Dorsal binding sites within cis-regulatory sequences was found to influence the domain of target-gene expression”

• cites Jiang and Levine 1993 sourceSupported

A gradient of activated Toll receptor was sufficient to support differential Dorsal target gene expression.

“This gradient of activated Toll receptor was sufficient to support differential Dorsaltarget gene expression.”

• cites Huang et al. 1997 sourceSupported

Ectopic expression experiments demonstrated that the dorsoventral axis can be reoriented such that genes normally expressed along the dorsoventral axis are instead expressed along the anteroposterior axis.

“These studies demonstrated that the DVaxis can be reoriented such that genes normally expressed along the DV axis are instead expressed along the AP axis”

• cites Huang et al. 1997 sourceSupported

Intermediate levels of nuclear Dorsal present in ventrolateral regions induce expression of genes such as rhomboid and ventral neuroblasts defective, which are important for specification of the neurogenic ectoderm.

“Intermediate levels of nuclear Dorsal, present in ventrolateral regions, induce the expression of genes such as rhomboid (rho) and ventral neuroblasts defective (vnd), which are important for specification of the neurogenic ectoderm”

• cites Bier et al. 1990 sourcePartly supported

  The Expression patterns of rho section (page unavailable) reports rho expression in ventrolateral domains, and the introductory section (page unavailable) links ventrolateral genes, including rho, to neural development. The copy does not establish that intermediate levels of nuclear Dorsal induce this expression, and it does not identify ventral neuroblasts defective (vnd) as another induced gene. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Ip et al. 1992aNot matched

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

• cites Jimenez et al. 1995 sourceNot checked — no full text of the source

A twi cis-regulatory sequence that normally directs expression to ventral regions exhibited a dorsally expanded expression domain when the low affinity Dorsal binding sites were mutated to high-affinity ones.

“A twi cis-regulatory sequence, which normally directs expression to ventral regions of the embryo, exhibited a dorsally expanded expression domain (i.e., the ventrolateral domain) when the low affinity Dorsal binding sites were mutated to highaffinity ones.”

• cites Jiang and Levine 1993 sourcePartly supported

  The Mechanism of repression section (page unavailable) says the twi promoter has low-affinity Dorsal sites and is activated in ventral regions. It does not report replacing those sites with high-affinity ones or a dorsally expanded twi expression domain. Instead, it describes the reverse substitution in the zen VRE. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

The organization of sites relative to each other, in particular the relationship between Dorsal and Twist transcription factors, may be important to support expression in given domains.

“Further analysis of cis-regulatory region architecture suggested that the organization of sites relative to each other, in particular of the relationship between Dorsal and Twist transcription factors, may be important to support expression in given domains”

• cites Jiang and Levine 1993 sourcePartly supported

  The Introduction (page unavailable) says that Dorsal’s effect depends on neighboring binding sites, and the Modes of repression section says nearby coactivators can help Dorsal activate transcription. But this paper does not identify a particular spatial relationship between Dorsal and Twist protein binding sites; its discussion of the twist promoter concerns sites bound by Dorsal. That specific part of the claim is unsupported. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites Erives and Levine 2004 sourceNot checked — no full text of the source
• cites Papatsenko and Levine 2005 sourceNot checked — no full text of the source

FGF signaling likely functions at multiple steps during mesoderm migration to control the directed movement of cells.

“FGF signaling likely functions at multiple steps during the migration to control the directed movement of cells (McMahon et al. 2008;Kadam et al. 2009).”

• cites McMahon et al. 2008 sourcePartly supported

  The supplied passages (indexed under Abstract; page unavailable) show that FGF signaling contributes to mesoderm migration: loss of signaling disrupts furrow collapse and angular spreading. But the paper identifies furrow collapse as FGF’s primary function and says another signal guides directed angular migration, so it does not establish that FGF acts at multiple steps to control that directed movement. (LLM, conf=0.85)

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

The ind gene is refined by the action of localized activators (downstream of EGFR signaling) and repressors.

“However, the ind gene is refined by the action of localized activators (i.e., downstream of EGFR signaling) and repressors.”

• cites Cowden and Levine 2003 sourcePartly supported

  The sections “A repression cascade patterns the neuroectoderm” and “Dorsal prepatterns the neuroectoderm” support repression of ind by localized factors and a role for EGF signaling in ind expression (page unavailable in our copy). They do not establish that localized activators downstream of EGFR refine ind; the latter section says it is unclear whether Dorsal activates ind directly or acts through EGF signaling. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Stathopoulos and Levine 2005bNot matched

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

In the Bicoid patterning system, absolute concentration thresholds of Bicoid are not the only determinate factors.

“In another example involving the Bicoid patterning system, a recent study of gradient interpretation directly shows that absolute concentration thresholds of Bicoid are not the only determinate factors in this system, likely because there are multiple spatially dependent inputs to Bicoid target genes (see hypothetical scenario in Fig. 5B) (Ochoa-Espinosa et al. 2009).”

• cites Ochoa-Espinosa et al. 2009 sourceSupported

ChIP-chip analyses with Dorsal, Snail, and Twist antibodies reveal strong binding peaks for one or more of these proteins in several AP patterning genes.

“ChIP-chip analyses with Dorsal, Snail, and Twist antibodies reveal strong binding peaks (left) for one or more of these proteins in several AP patterning genes.”

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

Multiple inputs exist to control the expression of genes along the DV axis.

“which shows that multiple inputs exist to control the expression of genes along the DV axis (Figs. 2 and 3)”

Genome-level studies increased knowledge of Dorsal target genes and enhancers roughly fivefold, from 10 to 50 target genes.

“Genomelevel studies have increased this knowledge fivefold, from the standpoint of numbers of target genes and numbers of enhancers known.”

• Also stated in: § CONCLUDING REMARKS · plain

  “The number of known Dorsal target genes increased roughly fivefold, from 10 to 50, through the use of genomic approaches.”

Different levels of Bicoid and Dorsal control the expression of distinct sets of genes.

“Different levels of these factors control the expression of distinct sets of genes.”

The positional information guiding activation of Toll is initiated by the follicle cells surrounding the developing oocyte during Stage 10 of oogenesis.

“The positional information guiding activation of Toll is initiated by the follicle cells surrounding the developing oocyte during Stage 10 of oogenesis”

• cites Anderson 1998 sourceNot checked — no full text of the source

Recent in vivo imaging studies using a Dorsal-GFP fusion protein show a constant shuttling of the protein between the cytoplasm and the nuclei, including the dorsal-most nuclei.

“recent in vivo imaging studies using a Dorsal-GFP fusion protein show a constant shuttling of the protein between the cytoplasm and the nuclei, including the dorsal-most nuclei”

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

Within the nuclei of early Drosophila embryos, the Dorsal transcription factor is present in a ventral-to-dorsal gradient.

“Within the nuclei of early Drosophila embryos, the Dorsal transcription factor is present in a ventral-to-dorsal gradient”

• cites Moussian and Roth 2005 sourceNot checked — no full text of the source

The maternally supplied Dorsal transcript is distributed and translated uniformly throughout the embryo.

“The maternally supplied Dorsal transcript is distributed and translated uniformly throughout the embryo;”

The gradient of nuclear-localized Dorsal regulates a number of genes in a concentration-dependent manner.

“The gradient of nuclear-localized Dorsal regulates a number of genes in a concentrationdependent manner”

• cites Stathopoulos and Levine 2004 sourceNot checked — no full text of the source

A gradient of Dorsal activity patterns the dorsoventral axis of the early Drosophila melanogaster embryo by controlling expression of genes that delineate presumptive mesoderm, neuroectoderm, and dorsal ectoderm.

“A gradient of Dorsal activity patterns the dorsoventral (DV) axis of the early Drosophila melanogaster embryo by controlling the expression of genes that delineate presumptive mesoderm, neuroectoderm, and dorsal ectoderm.”

At Stage 10, epidermal growth factor receptor signaling through the ligand Gurken limits expression of the gene pipe to the ventral-most follicle cells.

“At this stage, epidermal growth factor receptor (EGFR) signaling through the ligand Gurken limits expression of the gene pipe to the ventral-most follicle cells”

• cites Schupbach 1987 sourceNot checked — no full text of the source
• cites Sen et al. 1998 sourceNot checked — no full text of the source

The gradient of active Spatzle is further shaped through the action of a serpin, Spn27A.

“the gradient of active Spz is further shaped through the action of a serpin (serine-protease inhibitor), Spn27A”

• cites Hashimoto et al. 2003 sourceNot checked — no full text of the source
• cites Ligoxygakis et al. 2003 sourceNot checked — no full text of the source

Exclusion of Dorsal from nuclei is not achieved by simply preventing Dorsal nuclear import, but by a balance between slow import and rapid export.

“Therefore, it appears that exclusion of Dorsal from nuclei is not achieved by simply preventing Dorsal nuclear import, but by a balance between slow import and rapid export.”

Based on their expression patterns along the dorsoventral axis, the first set of 25 cis-regulatory sequences were categorized into four classes: ventral (Type I), ventrolateral (Type II), broad lateral (Type III+), and dorsal (Type III-) domains.

“Based on their expression patterns along the DV axis, this first set of 25 cis-regulatory sequences were categorized into four classes: ventral (Type I), ventrolateral (Type II), broad lateral (Type IIIþ), and dorsal (Type III2) domains”

• cites Stathopoulos and Levine 2004 sourceNot checked — no full text of the source

Different levels of activated Toll direct graded Dorsal-dependent gene expression outputs.

“Different levels of activated Toll direct graded Dorsal-dependent gene expression outputs.”

• cites Anderson et al. 1985 sourceNot checked — no full text of the source
• cites Stathopoulos et al. 2002Not matched

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

Bioinformatic approaches rapidly identified an additional 20 cis-regulatory sequences for genes expressed along the dorsoventral axis.

“Bioinformatic approaches rapidly identified an additional 20 cis-regulatory sequences for genes expressed along the DV axis.”

• cites Markstein et al. 2002 sourceNot checked — no full text of the source
• cites Stathopoulos et al. 2002Not matched

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

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

Like activin-dependent receptor signaling in Xenopus, cells in the early embryo are responsive to different levels of activated Toll receptor.

“Thus, like activindependent receptor signaling in Xenopus (Dyson and Gurdon 1998), it appears that cells in the early embryo are responsive to different levels of activated Toll receptor.”

• cites Dyson and Gurdon 1998 sourceNot checked — no full text of the source

Both Twist and Snail have been shown to bind the CACATGT site.

“whereas both Twist and Snail have been shown to bind the CACATGT site”

• cites Ip et al. 1992aNot matched

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

The Torso receptor tyrosine kinase signaling pathway, which is activated at the poles, selectively masks the ability of Dorsal to function as a transcriptional repressor at these positions.

“the Torso receptor tyrosine kinase signaling pathway, which is activated at the poles, selectively masks the ability of Dorsal to function as a transcriptional repressor at these positions”

• cites Rusch and Levine 1994 sourceNot checked — no full text of the source

Torso signaling modulates the ability of Capicua, Cut, and Dri to function, proteins that influence the ability of Dorsal to function as a transcriptional repressor.

“Torso signaling modulates the ability of Capicua (Cic), Cut, and Dri to function, proteins that influence the ability of Dorsal to function as a transcriptional repressor”

• cites Valentine et al. 1998 sourceNot checked — no full text of the source
• cites Jimenez et al. 2000 sourceNot checked — no full text of the source

dpp, tld, and zen are required for proper patterning of the dorsal ectoderm and amnioserosa, which develops in the dorsal-most regions of the embryo.

“These genes are required for proper patterning of the dorsal ectoderm and amnioserosa, which develops in the dorsal-most regions of the embryo”

• cites Rushlow and Levine 1990 sourceNot checked — no full text of the source
• cites Ferguson and Anderson 1992bNot matched

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

• cites Ferguson and Anderson 1992aNot matched

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

Low levels of nuclear Dorsal activate genes such as short-gastrulation and thisbe in broad lateral domains across the embryo.

“Low levels of nuclear Dorsal activate genes such as short-gastrulation (sog) and thisbe (ths) in broad lateral domains across the embryo”

• cites Markstein et al. 2002 sourceNot checked — no full text of the source
• cites Stathopoulos et al. 2002Not matched

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

To restrict rho expression to ventrolateral stripes in the embryo, Dorsal and Twist activation is antagonized in ventral regions by the Snail repressor, resulting in the lateral stripe pattern of gene expression.

“to restrict rho expression to ventrolateral stripes in the embryo, Dorsal and Twist activation is antagonized in ventral regions by the Snail repressor, resulting in the lateral stripe pattern of gene expression exhibited by these genes”

• cites Kosman et al. 1991 sourceNot checked — no full text of the source
• cites Ip et al. 1992aNot matched

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

All genes differentially expressed along the dorsoventral axis could be categorized into six basic patterns of gene expression.

“Surprisingly, all genes differentially expressed along the DV axis could be categorized into six basic patterns of gene expression”

CACATGT and RGGNCAG motifs were identified in enhancers supporting expression in ventrolateral stripes.

“In contrast, CACATGT and RGGNCAG motifs were identified in enhancers supporting expression in ventrolateral stripes”

• cites Stathopoulos et al. 2002Not matched

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

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

sog and ths genes are required for patterning the dorsal ectoderm, amnioserosa, and dorsal mesoderm.

“These genes are required for patterning the dorsal ectoderm, amnioserosa, and dorsal mesoderm”

• cites Francois et al. 1994 sourceNot checked — no full text of the source
• cites Stathopoulos et al. 2004Not matched

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

Following publication of the Drosophila genome, bioinformatic studies revealed the three principles of Dorsal-mediated patterning to be general.

“Following publication of the Drosophila genome, bioinformatic studies revealed these principles to be general.”

The same low levels of Dorsal that activate genes in lateral regions of the embryo also mediate repression of certain targets, such as decapentaplegic, tolloid, and zerknullt, thereby limiting their expression to regions where nuclear Dorsal is absent.

“The same low levels of Dorsal that activate genes in lateral regions of the embryo also mediate repression of certain targets, such as decapentaplegic (dpp), tolloid (tld), and zerknu ¨llt (zen), thereby limiting their expression to regions where nuclear Dorsal is absent”

• cites Ip et al. 1991Not matched

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

• cites Huang et al. 1993 sourceNot checked — no full text of the source
• cites Kirov et al. 1994 sourceNot checked — no full text of the source

This migration is required for subsequent differentiation of the mesoderm into distinct cell types.

“This migration is required for subsequent differentiation of the mesoderm into distinct cell types such as”

These studies suggested extensive cross talk between dorsoventral and anteroposterior patterning.

“These studies also suggested extensive cross talk between DV and AP patterning”

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

The enhancers for sim and m8 contain many transcription factor binding sites also found in Type II enhancers.

“However, the enhancers for sim and m8 contain many transcription factor binding sites also found in Type II enhancers.”

• cites Kasai et al. 1998Not checked — no full text of the source
• cites Stathopoulos and Levine 2005bNot matched

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

• cites Zinzen et al. 2006aNot matched

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

The FGF receptor Heartless and its two ligands Pyramus and Thisbe are all Dorsal targets.

“The FGF receptor (FGFR), Heartless (Htl), and its two ligands-Pyramus (Pyr) and Thisbe (Ths)-are all Dorsal targets”

• cites Stathopoulos et al. 2004Not matched

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

Analysis of the gene-regulatory network reveals that the Drosophila embryo uses different mechanisms to establish domains of expression.

“Analysis of this network reveals that the Drosophila embryo uses different mechanisms to establish domains of expression.”

htl expression requires peak levels of nuclear Dorsal and/or Twist.

“htl expression requires peak levels of nuclear Dorsal and/or Twist”

• cites Stathopoulos et al. 2004Not matched

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

Roughly half of the estimated Dorsal target genes encode signaling molecules.

“Roughly half of the estimated Dorsal target genes encode signaling molecules.”

• cites Stathopoulos and Levine 2004 sourceNot checked — no full text of the source

Several signaling pathways become active immediately following cellularization.

“In contrast, it has been shown that several signaling pathways become active immediately following cellularization.”

Patterning in a cellularized environment relies heavily on cell-cell communication coupled to signal transduction.

“This stands in contrast to patterning in a cellularized environment, which relies heavily on cell -cell communication coupled to signal transduction”

Twist and Snail transcription factors play an instrumental role in controlling invagination and ventral furrow formation by regulated expression of the genes folded-gastrulation, concertina, and T48.

“Twist and Snail transcription factors play an instrumental role in controlling invagination and ventral furrow formation by regulated expression of the genes folded-gastrulation, concertina, and T48”

• cites Parks and Wieschaus 1991 sourceNot checked — no full text of the source
• cites Dawes-Hoang et al. 2005 sourceNot checked — no full text of the source
• cites Sandmann et al. 2007 sourceNot checked — no full text of the source

Hundreds of newly predicted cis-regulatory regions were found throughout the genome, based on the assumption that occupancy of a factor on the DNA is associated with changes in gene expression observed for nearby genes.

“Hundreds of newly predicted cisregulatory regions were found throughout the genome, based on the assumption that occupancy of a factor on the DNA is associated with changes in gene expression observed for nearby genes.”

• AssumptionThe authors state this as an assumption: Occupancy of a factor on the DNA is associated with changes in gene expression observed for nearby genes.

Tiling arrays identified specific, differentially expressed splice products (e.g., bunched) and miRNAs (mir1 and mir9a) that could not be distinguished with standard arrays containing probes designed only to assay predicted gene products.

“the tiling arrays also identified specific, differentially expressed splice products (e.g., bunched) and miRNAs (mir1 and mir9a), that could not be distinguished with standard arrays containing probes designed only to assay predicted gene products.”

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

These cells then proceed to migrate along the ectodermal cells toward dorsal regions of the embryo.

“These cells then proceed to migrate along the ectodermal cells toward dorsal regions of the embryo”

Tiling arrays increased the number of genes exhibiting Dorsal-dependent regulation from approximately 50 predicted by standard chip hybridizations to approximately 100.

“Besides increasing the number of genes exhibiting Dorsal-dependent regulation from approximately 50 predicted by standard chip hybridizations (Stathopoulos et al. 2002) to approximately 100 (Biemar et al. 2006)”

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

Patterning is initiated when the embryo itself is a syncytium, an unusual aspect of Drosophila embryogenesis.

“In addition, patterning is initiated when the embryo itself is a syncytium, an unusual aspect of Drosophila embryogenesis.”

Other ChIP-chip analyses conducted in the early Drosophila embryo showed that the occupancy of genomic sites by most transcription factors is extensive.

“Furthermore, other ChIP-chip analyses conducted in the early Drosophila embryo showed that the occupancy of genomic sites by most transcription factors is extensive”

• cites Li et al. 2008Not matched

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

Feedforward loops, such as the requirement of the Dorsal-target gene Twist to turn on the repressor Snail, function as timing mechanisms that ensure that genes are expressed in proper sequence.

“Feedforward loops, such as the requirement of the Dorsal-target gene, Twist, to turn on the repressor Snail, function as timing mechanisms that ensure that genes are expressed in proper sequence.”

Together, these repressors restrict ind to its lateral expression domain.

“Together, these repressors restrict ind to its lateral expression domain”

ChIP-chip methodology identified in vivo binding site occupancy for Dorsal, Twist, and Snail transcription factors.

“Experiments to identify cis-regulatory regions using ChIP-chip methodology were able to identify in vivo binding site occupancy for Dorsal, Twist, and Snail transcription factors”

• cites Sandmann et al. 2007 sourceNot checked — no full text of the source
• cites Zeitlinger et al. 2007 sourceNot checked — no full text of the source

This results in an epithelial-to-mesenchymal transition of the presumptive mesodermal cells located in the interior of the embryo.

“This results in an epithelial-to-mesenchymal transition (EMT) of the presumptive mesodermal cells located in the interior of the embryo.”

The common cytoplasm of the Drosophila syncytium permits the formation of transcription-factor gradients, which can directly act on gene-expression outputs.

“The common cytoplasm of the Drosophila syncytium permits the formation of transcriptionfactor gradients, which can directly act on gene-expression outputs.”

A single-morphogen model fails to account for the remarkable insensitivity of developmental patterns with respect to many natural and experimental perturbations to the system.

“In particular, a singlemorphogen model fails to account for the remarkable insensitivity of developmental patterns with respect to many natural and experimental perturbations to the system (see Fig. 5A).”

Multiple levels of regulation on target gene expression are a necessary condition for developmental reliability.

“However, this is simply a necessary condition for developmental reliability.”

It is likely that absolute concentration thresholds are not the only determinate factors in the Dorsal patterning system.

“This is likely to be the case in light of the current evidence, which shows that multiple inputs exist to control the expression of genes along the DV axis (Figs. 2 and 3) and that compensatory mechanisms may support expression in mutant backgrounds that show decreased Dorsal levels (Stathopoulos and Levine 2002b).”

• cites Stathopoulos and Levine 2002bNot matched

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

The key to differential gene expression is combinatorial regulation through the interaction of multiple transcription factors.

“Thus, the key to differential gene expression is combinatorial regulation through the interaction of multiple transcription factors.”

The absolute levels of Dorsal are less important than the sum total of several factors present within nuclei, integrated in a complex manner at each individual enhancer site.

“This would imply that the absolute levels of Dorsal are less important than the sum total of several factors present within nuclei, integrated in a complex manner at each individual enhancer site (see Fig. 5B).”

Compensatory mechanisms may support expression in mutant backgrounds that show decreased Dorsal levels.

“and that compensatory mechanisms may support expression in mutant backgrounds that show decreased Dorsal levels (Stathopoulos and Levine 2002b).”

• cites Stathopoulos and Levine 2002bNot matched

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

Dorsal activity along the dorsoventral axis initiates a cascade of repressors.

“Dorsal activity along the dorsoventral (DV) axis initiates a cascade of repressors (upper panel).”

In addition to FGF signaling, TGF-b signaling is required to induce mesoderm cells that reach the dorsal-most regions of the ectoderm to adopt cardial and dorsal somatic mesoderm lineage choices.

“For instance, in addition to FGF signaling, TGF-b signaling is also required to induce mesoderm cells that reach the dorsal-most regions of the ectoderm to adopt cardial and dorsal somatic mesoderm lineage choices (Fig. 4B).”

• cites Stathopoulos and Levine 2004 sourceNot checked — no full text of the source

Once mesoderm cells reach the dorsal ectoderm, multiple signaling inputs control which differentiation programs are adopted.

“As a result of this coordinated migration, once mesoderm cells reach the dorsal ectoderm, multiple signaling inputs control which differentiation programs are adopted.”

Dorsal regulates the activation of the TGF-b, EGFR, and FGF signaling pathways by spatial regulation of pathway components.

“Dorsal regulates the activation of the TGF-b, EGFR, and FGF signaling pathways by spatial regulation of pathway components.”

• cites Stathopoulos and Levine 2004 sourceNot checked — no full text of the source

A lone morphogen is not sufficient to explain developmental patterning.

“The existence of this regulation is not surprising, as physical arguments show that a lone morphogen is not sufficient to explain developmental patterning (Lander 2007;Jaeger et al. 2008).”

• cites Lander 2007 sourceNot checked — no full text of the source
• cites Jaeger et al. 2008 sourceNot checked — no full text of the source

Any viable model of morphogen-mediated patterning must include multiple levels of regulation on target gene expression.

“Therefore, any viable model of morphogen-mediated patterning must include multiple levels of regulation on target gene expression (see Figs. 2 and 3).”