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Cited by 166Developmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanismsCongenital heart defects research

Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network

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de Crozé, Noémie, Maczkowiak, Frédérique, Monsoro-Burq, Anne H.·2011·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1010740107PMC PMC3017139
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Abstract

The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC emergence; however, the role of AP2 factors at the NB remains unclear. We show here that AP2a initiates NB patterning and is sufficient to elicit a NB-like pattern in neuralized ectoderm. In contrast, the other early regulators do not participate in ap2a initiation at the NB, but cooperate to further establish a robust NB pattern. The NC regulatory network uses a multistep cascade of secreted inducers and transcription factors, first at the NB and then within the NC progenitors. Here we report that AP2a acts at two distinct steps of this cascade. As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB and activate pax3 ; as a NC specifier, AP2a regulates further NC development independent of and downstream of NB patterning. Our findings reconcile conflicting observations from various vertebrate organisms. AP2a provides a paradigm for the reiterated use of multifunctional molecules, thereby facilitating emergence of the NC in vertebrates.

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Crossref · 10.1073/pnas.1010740107

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  • BAZ1B binding regions are enriched for target sites of major regulators of neural crest and its neural derivatives, among which TFAP2A stands out given its core role in neural border formation and neural crest induction and differentiation through binding and stabilization of neural-crest-specific enhancers with NR2F1, NR2F2, and EP300.

    “Thus, BAZ1B binding regions are enriched for target sites of major regulators of NC and its neural derivatives (38, 39), among which TFAP2A stands out given its core role in neural border formation and NC induction and differentiation (40) through the binding and stabilization of NC-specific enhancers, in concert with NR2F1, NR2F2, and EP300 (41).”

    From Dosage analysis of the 7q11.23 Williams region identifies <i>BAZ1B</i> as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [40]

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Authors
de Crozé, N., Maczkowiak, F., & Monsoro-Burq, A. H.
Affiliations
  • Institut Curie, Institut National de la Santé et de la Recherche Médicale U1021, Centre National de la Recherche Scientifique Unité Mixte de Recherche 3347, F-91405 Orsay, France; and
  • Université Paris-Sud (FR)
ORCID
Monsoro-Burq, Anne H.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2010-12-15
Volume
108
Issue
1
Pages
155-160
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1010740107
PMC
PMC3017139
OpenAlex
W2056208399
Cited by
166
References
34
Citations by year
2026: 8 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 12 · 2020: 15 · 2019: 15 · 2018: 13 · 2017: 12 · 2016: 8 · 2015: 13 · 2014: 12 · 2013: 11 · 2012: 18
FWCI
4.69
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
neural crest, gene regulatory networks, Wnt signaling, Pax3, transcription factors, neural crest specification, vertebrate evolution
MeSH terms
PAX3 Transcription Factor, Animals, Epistasis, Genetic, Humans, Models, Biological, Neural Crest, Transcription Factors, Xenopus laevis, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, Xenopus Proteins, Transcription Factor AP-2, Paired Box Transcription Factors, Gene Regulatory Networks, Gene Knockdown Techniques

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