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Cited by 93Developmental Biology and Gene RegulationGenomics and Chromatin DynamicsMarine Invertebrate Physiology and Ecology

Transphyletic conservation of developmental regulatory state in animal evolution

Open access
Royo, José Luis, Maeso, Ignacio, Irimia, Manuel, Gao, Feng, Peter, Isabelle S., Lopes, Carla S., D'Aniello, Salvatore, Casares, Fernando +3 more·2011·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1109037108PMC PMC3161536
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Abstract

Specific regulatory states, i.e., sets of expressed transcription factors, define the gene expression capabilities of cells in animal development. Here we explore the functional significance of an unprecedented example of regulatory state conservation from the cnidarian Nematostella to Drosophila , sea urchin, fish, and mammals. Our probe is a deeply conserved cis -regulatory DNA module of the SRY-box B2 ( soxB2 ), recognizable at the sequence level across many phyla. Transphyletic cis -regulatory DNA transfer experiments reveal that the plesiomorphic control function of this module may have been to respond to a regulatory state associated with neuronal differentiation. By introducing expression constructs driven by this module from any phyletic source into the genomes of diverse developing animals, we discover that the regulatory state to which it responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain. The regulatory state recognized by the conserved DNA sequence may have been redeployed to different levels of the developmental regulatory program during evolution of complex central nervous systems.

Verified 2026-10-06 · 4 references not checked yet

AI snapshot

Written from the paper’s full text.

TL;DR

A deeply conserved cis-regulatory module near soxB2/sox21, recognizable from cnidarians to vertebrates, responds to a conserved neuronal regulatory state. Transphyletic transgenic assays show this state has been redeployed at different levels of nervous system development, from neuronal differentiation to forebrain patterning and Drosophila neuroblast proliferation.

Key findings

  • A conserved noncoding region (CNR) at the soxB2/sox21 locus was identified across human, zebrafish, amphioxus, sea urchin, hemichordate, and the cnidarian Nematostella; seven additional CNRs, 76–217 bp long, were conserved in chordate and nonchordate deuterostomes, with one also recognizable in Nematostella.
  • Transgenic reporter assays showed soxB2 CNRs from diverse phyla drive expression in developing zebrafish CNS regions (forebrain, eye, midbrain, hindbrain, spinal cord); at 24 h, human and sea urchin constructs also expressed in midbrain, the sea urchin construct had an additional diencephalon domain, and the Nematostella construct did not express in midbrain.
  • The same CNRs drove expression in sea urchin ciliary band neurons and in Drosophila larval CNS neuroblasts and optic lobes, indicating that key components of the regulatory state are present across large phylogenetic distances.
  • Morpholino knockdown of zebrafish sox21a and sox21b (15 ng individual or 7.5 ng each together) did not affect GFP driven by human or sea urchin soxB2 CNR constructs, ruling out positive autoregulation by endogenous Sox21.

Methods

  • Computational scan for deeply conserved CNRs across eumetazoan genomes, using chordate CNRs as probes; the soxB2 CNR and seven additional CNRs were identified and functionally tested.
  • Transgenic reporter constructs were introduced into zebrafish (Tol2 system), sea urchin eggs (cytoplasmic injection), and Drosophila; expression was analyzed by whole-mount in situ hybridization, double in situ hybridization, and confocal immunofluorescence.
  • Morpholino knockdown of zebrafish sox21a and sox21b was used to test whether the CNRs are positively autoregulated by Sox21.

Limitations

  • Stated: 48-h zebrafish images do not afford cellular resolution, so expression comparisons pertain only to general regions; expression patterns were similar but not identical, with the sea urchin CNR apparently lacking a diencephalon repressor site and the Nematostella CNR apparently lacking sites for some regional brain activators.
  • Stated: the conserved SoxB2 CNRs cannot be detected in the genomes of a mollusk, an annelid, a crustacean, or Drosophila, so cross-phyletic function in Drosophila was tested despite no gross sequence similarity.
  • Evident: conclusions about ancestral regulatory state rely on heterologous transgenic reporter assays; no direct CNR loss-of-function is reported in most contexts, and sea urchin transgenesis is mosaic.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1073/pnas.1109037108

Cites

37 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 34 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Transphyletic conservation of developmental regulatory state in animal evolution · p. 1

    The regulatory state to which the soxB2 CNR responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain.

    “By introducing expression constructs driven by this module from any phyletic source into the genomes of diverse developing animals, we discover that the regulatory state to which it responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results · p. 4

    In the larval CNS of Drosophila, SpSoxB2-CNR and HsSOX21-CNR both drive expression in neuroblasts of the central brain and ventral nerve cord as well as in the optic lobes.

    “In the larval CNS, SpSoxB2 -CNR and HsSOX21 -CNR both drive expression in neuroblasts of the central brain and ventral nerve cord as well as in the optic lobes”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results · p. 1

    One of these CNRs also can be recognized in the Nematostella genome.

    “One of these CNRs also can be recognized in the Nematostella genome (Fig. S2 B ; for computational procedures and criterion of conservation see SI Materials and Methods ).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results · p. 4

    In transgenic Drosophila embryos, the human HsSOX21-CNR construct is expressed in a small subset of neuroblasts of the ventral nerve cord.

    “and, in addition, the human construct is expressed in a small subset of neuroblasts of the ventral nerve cord”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Discussion · p. 5

    With a couple of exceptions, in each transphyletic context the CNRs from diverse sources generate a very similar regulatory output.

    “With a couple of exceptions, in each transphyletic context the CNRs from diverse sources generate a very similar regulatory output.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 1
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 4

  • The quote only partly states this claim.

    Findingown data
    § Transphyletic conservation of developmental regulatory state in animal evolution · p. 1

    The soxB2 CNR is a deeply conserved cis-regulatory DNA module recognizable at the sequence level across many phyla, including human, zebrafish, amphioxus, sea urchin, Saccoglossus, and Nematostella.

    “Our probe is a deeply conserved cis -regulatory DNA module of the SRY-box B2 ( soxB2 ), recognizable at the sequence level across many phyla.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Transphyletic conservation of developmental regulatory state in animal evolution · p. 1

    The study shows that a very unusually conserved genomic regulatory sequence leads to conserved cell type-specific regulatory states, and that this regulatory state has been co-opted functionally during evolution, at least in part, for use in different levels of the developmental regulatory process.

    “Here, we follow a trail that leads from a very unusually conserved genomic regulatory sequence to conserved cell type-speci fi c regulatory states, but we also show that this regulatory state has been co-opted functionally during evolution, at least in part, for use in different levels of the developmental regulatory process.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 2

    In spinal cord sections, sox21 is expressed through almost all the cross-sectional area, as are the human CNR construct and, to a lesser extent, the sea urchin construct.

    “In the spinal cord sections it can be seen that sox21 is expressed through almost all the cross-sectional area (Fig. 2 E Inset , H , K ), as are the human CNR construct (Fig. 2 I ) and, to a lesser extent, the sea urchin construct (Fig. 2 L ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 3

    At the 5-15 somite stage, neurogenesis has commenced in the forebrain, but the human, sea urchin, and Nematostella soxB2 CNR constructs are expressed much more widely, including regions where there still is no neurogenin expression posterior to the pax2 stripe.

    “At the 5 -15 somite stage, neurogenesis has commenced in the forebrain (Fig. 3 D Inset ), but the human, sea urchin, and Nematostella soxB2 CNR constructs are expressed much more widely, including regions where there still is no neurogenin expression posterior to the pax2 stripe (Fig. 3 E -H and Fig. S5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 2

    At the 48-h stage, the hemichordate and Nematostella CNR constructs are expressed less robustly, although all are clearly positive in the forebrains of the transgenic fish.

    “At the 48-h stage the hemichordate and Nematostella CNR constructs are expressed less robustly, although all are clearly positive in the forebrains of the transgenic fi sh (Fig. S4 C -D ).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 4

    Both human and sea urchin soxB2 CNR expression constructs are expressed strongly and specifically in the late embryonic and third-instar larval CNS of Drosophila.

    “Both constructs are expressed strongly and speci fi cally in the late embryonic and the third-instar larval CNS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 4

    Conserved SoxB2 CNRs are not detectable in the genomes of the mollusk Lottia, the annelid Capitella, the crustacean Daphnia, or Drosophila, and may not be conserved at the gross sequence level in any protostome genome.

    “The conserved SoxB2 CNRs cannot be detected in the genomes of a mollusk ( Lottia ), an annelid ( Capitella ), a crustacean ( Daphnia ), or in the Drosophila genome, and perhaps it is not conserved at the gross sequence level, as in Fig. 1, in any protostome genome.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 3

    The human SOX21 CNR construct is expressed like the endogenous zebrafish sox21b, whereas the sea urchin construct is expressed over all the anterior neuroepithelium.

    “The human SOX21 CNR construct is expressed like the endogenous zebra fi sh sox21b , whereas the sea urchin construct is expressed over all the anterior neuroepithelium (Fig. 3 B and C ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 2

    Although at least some small patches of mature neurons denoted by HuC expression overlap with GFP expression domains, most of the spinal cord sectional area where the CNRs are active lacks mature neurons.

    “Although at least some of the small patches of mature neurons denoted by HuC expression overlap with GFP expression domains, most of the spinal cord sectional area where the CNRs are active lacks mature neurons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 4

    When the sea urchin, human, or Nematostella soxB2 CNRs are inserted in expression vectors and injected into fertilized eggs, they are expressed in individual ciliary band neurons of the feeding larva and can be identified by GFP-stained axons.

    “When the sea urchin, human, or Nematostella soxB2 CNRs are inserted in expression vectors and injected into fertilized eggs, they also are expressed in individual ciliary band neurons of the feeding larva and can be identi fi ed by the GFP-stained axons (Fig. 4 B -D ; for empty vector controls, see Fig. S7 K -M ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 4

    The endogenous soxB2 of the sea urchin is expressed in feeding larvae in the heavily innervated ciliary band, as well as in cells of the midgut wall.

    “The endogenous soxB2 of the sea urchin is expressed in feeding larvae in the heavily innervated ciliary band, as well as in cells of the midgut wall, as shown by whole-mount FISH (Fig. 4 A ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 4

    In later stages of transgenic Drosophila embryos, the human HsSOX21-CNR construct is expressed in the peripheral nervous system chordotonal organs and in dorsal and ventral epidermis.

    “and, in later stages, in the peripheral nervous system chordotonal organs and in dorsal and ventral epidermis”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results · p. 2

    The human and sea urchin constructs express in midbrain as well, but the Nematostella construct does not.

    “However, the human and sea urchin constructs express in midbrain as well (Fig. 2 D and E ), but the Nematostella construct does not (Fig. 2 F ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation
    § Results · p. 4

    The sea urchin CNR is active in the inner proliferative center of the optic lobes, which gives rise to inner medulla and lobulla neurons, and in the outer proliferative region, which develops into lamina and outer medulla neurons.

    “Here we see that the sea urchin CNR is active in the inner proliferative center of the optic lobes, which will give rise to inner medulla and lobulla neurons, and also in the outer proliferative region, which develops into lamina and outer medulla neurons (32).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Meinertzhagen IA, Hanson JA (1993). The development of the optic lobe. The Development of Drosophila melanogaster, eds M. Bate and A. Martinez-Arias (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY), pp. 1363 -1491.

      Not checked in the free run.

  • May combine two claims.

    Findingown data
    § Results · p. 2

    At 24 h, all three constructs (human, sea urchin, Nematostella) express clearly in the anterior forebrain, as does the endogenous sox21b gene.

    “All, including the Nematostella construct, express clearly in the anterior forebrain (Fig. 2 D -F ), as does the endogenous sox21b gene (Fig. 2 G , J , M ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion · p. 5

    In zebrafish, the soxB2 CNRs become active before neurogenesis, perhaps in forebrain pattern formation, and their function then extends to some mature neurons in the spinal cord.

    “In zebra fi sh, however, the soxB2 CNRs become active before neurogenesis, perhaps in forebrain pattern formation, and their function then extends to some mature neurons in the spinal cord (Figs. 4 and 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Results · p. 4

    In sea urchin, injected DNA is incorporated stably and randomly in all cell lineages, but in a mosaic fashion.

    “In this organism, injected DNA is incorporated stably and randomly in all cell lineages, but in a mosaic fashion (31).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Livant DL, Hough-Evans BR, Moore JG, Britten RJ, Davidson EH (1991) Differential stability of expression of similarly speci fi ed endogenous and exogenous genes in the sea urchin embryo. Development 113:385 -398.

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given
    § Discussion · p. 5

    The conserved sequence elements seen in Fig. 1B suffice to interact with a number of different transcription factors, and together these factors constitute the regulatory state to which they respond.

    “The conserved sequence elements seen in Fig. 1 B obviously suf fi ce to interact with a number of different TFs, and together these factors constitute the regulatory state to which they respond.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Transphyletic conservation of developmental regulatory state in animal evolution · p. 1

    The immune cells of sea urchins, lampreys, and amniotes use entirely different receptor proteins, but their deployment is controlled by homologous regulatory states in all three cases.

    “For example, the immune cells of sea urchins, lampreys, and amniotes use entirely different receptor proteins, but their deployment is controlled by homologous regulatory states in all three cases (18 -20).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] Herrin BR, Cooper MD (2010) Alternative adaptive immunity in jawless vertebrates. J Immunol 185:1367 -1374. source

      Not checked in the free run.

    • cites [19] Hibino T, et al. (2006) The immune gene repertoire encoded in the purple sea urchin genome. Dev Biol 300:349 -365. source

      Not checked in the free run.

    • cites [20] Messier-Solek C, Buckley KM, Rast JP (2010) Highly diversi fi ed innate receptor systems and new forms of animal immunity. Semin Immunol 22:39 -47. of SI Materials and Methods and Tables S1 and S2 contains the detailed procedures by which the CNRs were cloned and built into expression vectors. For insertion into sea urchin eggs, the vectors were injected into egg cytoplasm; for insertion into zebra fi sh, the Tol2 system was used as described in SI Materials and Methods and the references therein. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Transphyletic conservation of developmental regulatory state in animal evolution · p. 1

    Given regulatory states can be redeployed during evolution for use in developmental contexts other than immediate cell-type specification, and this redeployment probably is a major mechanism of evolutionary change in body plan.

    “Given regulatory states can be redeployed during evolution for use in developmental contexts other than immediate cell-type speci fi cation, this redeployment probably is a major mechanism of evolutionary change in body plan (22).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Gao F, Davidson EH (2008) Transfer of a large gene regulatory apparatus to a new developmental address in echinoid evolution. Proc Natl Acad Sci USA 105:6091 -6096. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Results · p. 2

    The sea urchin CNR is insensitive to a regional repression function, evidently lacking the requisite target sites.

    “but rather implies a regional repression function to which the sea urchin CNR is insensitive, evidently lacking the requisite target sites (Fig. 2 G and J ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Results · p. 4

    At least key components of the regulatory state used plesiomorphically in differentiated sea urchin and vertebrate neurons are also expressed in the Drosophila brain and optic lobes, even though no sequence grossly similar to a soxB2 CNR exists in the Drosophila genome.

    “The main conclusion from Fig. 5 is that at least key components of the regulatory state used plesiomorphically in differentiated sea urchin and vertebrate neurons also are expressed in the Drosophila brain and optic lobes, even though no sequence grossly similar to a soxB2 CNR exists in the Drosophila genome.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Transphyletic conservation of developmental regulatory state in animal evolution · p. 1

    The integument cells that are tasked with wound repair and building the outer epidermis of insects and vertebrates use entirely different effector genes, but these genes are driven by the same regulatory factor.

    “Similarly, the integument cells that are tasked with wound repair and building the outer epidermis of insects and vertebrates use entirely different effector genes, but these genes are driven by the same regulatory factor (21).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Pearson JC, Juarez MT, Kim M, Drivenes O, McGinnis W (2009) Multiple transcription factor codes activate epidermal wound-response genes in Drosophila . Proc Natl Acad Sci USA 106:2224 -2229. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning
    § Discussion · p. 5

    The last stage of a developmental process consists of the expression of differentiation gene batteries.

    “The last stage consists of the expression of differentiation gene batteries.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion · p. 5

    A developmental process, such as regional development of an element of the nervous system, can be considered as the outcome of a given hierarchical GRN.

    “A developmental process, such as the regional development of an element of the nervous system, can be considered as the outcome of a given hierarchical GRN(1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Peter IS, Davidson EH (2011) Evolution of gene regulatory networks controlling body plan development. Cell 144:970 -985. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Structural Implications of Evolutionary Regulatory State Redeployment. · p. 5

    Examples cited at the beginning of the article show that the regulatory state can be disassociated from its downstream targets, and new downstream targets can be inserted.

    “The examples cited at the beginning of this article in which the regulators controlling differentiation of a given cell type remain unchanged in evolution, although controlling different sets of effector genes, show that the regulatory state can be disassociated from its downstream targets, and new downstream targets can be inserted.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Structural Implications of Evolutionary Regulatory State Redeployment. · p. 5

    The idea of 'intercalary evolution' has been adduced to explain the utilization of given regulatory genes in both terminal differentiation gene batteries and upstream developmental GRNs.

    “The idea of ' intercalary evolution ' has been adduced to explain the utilization of given regulatory genes in both terminal differentiation gene batteries and upstream developmental GRNs (8, 41).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Davidson EH (2006) The Regulatory Genome. Gene Regulatory Networks in Development and Evolution (Academic/Elsevier, San Diego).

      Not checked in the free run.

    • cites [41] Gehring WJ, Ikeo K (1999) Pax 6: Mastering eye morphogenesis and eye evolution. Trends Genet 15:371 -377. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion · p. 5

    The regulatory state recognized by the soxB2 CNRs always has been generated by developmental GRNs of the nervous system, but during evolution this regulatory state has been used at altered hierarchical positions in the GRN.

    “Thus, the general answer to the questions above is that the regulatory state recognized by the soxB2 CNRs always has been generated by developmental GRNs of the nervous system, but during evolution this regulatory state has been used at altered hierarchical positions in the GRN.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § Structural Implications of Evolutionary Regulatory State Redeployment. · p. 5

    A key aspect of developmental regulatory evolution could be the redeployment of regulatory states from plesiomorphic roles as drivers of differentiation gene batteries to functions that in modern GRNs control earlier developmental processes.

    “A key aspect of developmental regulatory evolution could be the redeployment of regulatory states from plesiomorphic roles as drivers of differentiation gene batteries to functions that in modern GRNs control earlier developmental processes.”
    Quote in the paperSubstantial claim
29 of 29

  • The paper relies on this without support.

    Sea urchins have no forebrains, midbrains, spinal columns, eyes, or otic vesicles.

    “Sea urchins have no forebrains, midbrains, spinal columns, eyes, or otic vesicles.”
1 of 1

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Sea urchin larval expression cites the zebrafish figure

    Minor

    The Discussion attributes expression in transgenic sea urchin larvae to Fig. 2, but Fig. 2 is captioned as zebrafish experiments; the sea urchin larvae are shown in Fig. 4.

  • Figure 4 assigns conflicting panel letters to the Nematostella construct

    Minor

    The Results identify panels B-D as the sea urchin, human, and Nematostella constructs, but the Fig. 4 caption assigns the Nematostella construct to panel F.

  • Zebrafish developmental claims cite figures of other animals

    Minor

    The Discussion cites Figs. 4 and 5 for zebrafish expression, but their captions identify sea urchin larvae and larval Drosophila CNS, respectively.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. IA Meinertzhagen JA Hanson The development of the optic lobe. The Development of Drosophila melanogaster. eds M Bate A Martinez-Arias (Cold Spring Harbor Laboratory Press Cold Spring Harbor NY) pp. 1363–1491 (1993).

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Authors
Royo, J. L., Maeso, I., Irimia, M., Gao, F., Peter, I. S., Lopes, C. S., D'Aniello, S., Casares, F., Davidson, E. H., Garcia-Fernández, J., & Gómez-Skarmeta, J. L.
Affiliations
  • Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Cientificas - Universidad Pablo de Olavide, E-41013 Sevilla, Spain;
  • Institut de Biomedicina de la Universitat de Barcelona (ES)
  • California Institute of Technology (US)
  • Consejo Superior de Investigaciones Científicas (ES)
  • Departament de Genetica, and Institut de Biomedicina, Universitat de Barcelona, Barcelona E-08028, Spain; and
Corresponding author
Davidson, Eric H.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2011-08-15
Volume
108
Issue
34
Pages
14186-14191
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1109037108
PMC
PMC3161536
OpenAlex
W1977704866
Cited by
93
References
41
Citations by year
2026: 2 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 11 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 12 · 2014: 8 · 2013: 10 · 2012: 11
FWCI
3.76
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • National Institutes of Health (5p01hd037105-20)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 037105, P01-HD037105)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Physical Sciences › Earth and Planetary Sciences › Paleontology › Marine Invertebrate Physiology and Ecology
Keywords
cis-regulatory modules, neuronal differentiation, neurogenesis, forebrain patterning, optic lobe, central nervous system evolution, Nematostella, Drosophila, sea urchins, fish, mammals, gene expression evolution
MeSH terms
Animals, Base Sequence, Brain, Drosophila, Enhancer Elements, Genetic, Biological Evolution, Larva, Molecular Sequence Data, Phylogeny, Sea Urchins, Zebrafish, Conserved Sequence, Gene Expression Regulation, Developmental, DNA, Intergenic, Animals, Genetically Modified, SOXB2 Transcription Factors

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