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Dynamic and Differential Regulation of Stem Cell Factor FoxD3 in the Neural Crest Is Encrypted in the Genome

Simões-Costa, Marcos S. and McKeown, Sonja J. and Tan-Cabugao, Joanne and Sauka-Spengler, Tatjana and Bronner, Marianne E. (2012) Dynamic and Differential Regulation of Stem Cell Factor FoxD3 in the Neural Crest Is Encrypted in the Genome. PLoS Genetics, 8 (12). Art. No. e1003142. ISSN 1553-7390. PMCID PMC3527204. doi:10.1371/journal.pgen.1003142. https://resolver.caltech.edu/CaltechAUTHORS:20130131-095347879

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Abstract

The critical stem cell transcription factor FoxD3 is expressed by the premigratory and migrating neural crest, an embryonic stem cell population that forms diverse derivatives. Despite its important role in development and stem cell biology, little is known about what mediates FoxD3 activity in these cells. We have uncovered two FoxD3 enhancers, NC1 and NC2, that drive reporter expression in spatially and temporally distinct manners. Whereas NC1 activity recapitulates initial FoxD3 expression in the cranial neural crest, NC2 activity recapitulates initial FoxD3 expression at vagal/trunk levels while appearing only later in migrating cranial crest. Detailed mutational analysis, in vivo chromatin immunoprecipitation, and morpholino knock-downs reveal that transcription factors Pax7 and Msx1/2 cooperate with the neural crest specifier gene, Ets1, to bind to the cranial NC1 regulatory element. However, at vagal/trunk levels, they function together with the neural plate border gene, Zic1, which directly binds to the NC2 enhancer. These results reveal dynamic and differential regulation of FoxD3 in distinct neural crest subpopulations, suggesting that heterogeneity is encrypted at the regulatory level. Isolation of neural crest enhancers not only allows establishment of direct regulatory connections underlying neural crest formation, but also provides valuable tools for tissue specific manipulation and investigation of neural crest cell identity in amniotes.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pgen.1003142DOIArticle
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003142PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527204/PubMed CentralArticle
ORCID:
AuthorORCID
Simões-Costa, Marcos S.0000-0003-1452-7068
Sauka-Spengler, Tatjana0000-0001-9289-0263
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2012 Simões-Costa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received March 12, 2012; Accepted October 18, 2012; Published December 20, 2012. This work was supported by NIH grant HD037105 to MEB, a NHMRC CJ Martin Fellowship (400433) to SJM, and a Pew Foundation Fellowship to MSS-C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Hisato Kondoh for the ptk-eGFP construct, Mirella Dottori for FoxD3 in situ probe, and Patricia Labosky and Michelle Southard-Smith for the anti-FoxD3 antibody. We also thank Michael Stone and Brian Jun for excellent technical assistance. Author Contributions: Conceived and designed the experiments: MSS-C SJM TS-S MEB. Performed the experiments: MSS-C SJM JT-C TS-S. Analyzed the data: MSS-C SJM TS-S MEB. Wrote the paper: MSS-C SJM TS-S MEB.
Funders:
Funding AgencyGrant Number
NIHHD037105
National Health and Medical Research Council (NHMRC)400433
Pew FoundationUNSPECIFIED
Issue or Number:12
PubMed Central ID:PMC3527204
DOI:10.1371/journal.pgen.1003142
Record Number:CaltechAUTHORS:20130131-095347879
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130131-095347879
Official Citation:Simões-Costa MS, McKeown SJ, Tan-Cabugao J, Sauka-Spengler T, Bronner ME (2012) Dynamic and Differential Regulation of Stem Cell Factor FoxD3 in the Neural Crest Is Encrypted in the Genome. PLoS Genet 8(12): e1003142. doi:10.1371/journal.pgen.1003142
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:36709
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:31 Jan 2013 19:25
Last Modified:09 Nov 2021 23:24

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