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Human ESC-Derived Neural Crest Model Reveals a Key Role for SOX2 in Sensory Neurogenesis

Cimadamore, Flavio and Fishwick, Katherine and Giusto, Elena and Gnedeva, Ksenia and Cattarossi, Giulio and Miller, Amber and Pluchino, Stefano and Brill, Lawrence M. and Terskikh, Alexey V. and Bronner-Fraser, Marianne (2011) Human ESC-Derived Neural Crest Model Reveals a Key Role for SOX2 in Sensory Neurogenesis. Cell Stem Cell, 8 (5). pp. 538-551. ISSN 1934-5909. PMCID PMC4110917.

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The transcription factor SOX2 is widely known to play a critical role in the central nervous system; however, its role in peripheral neurogenesis remains poorly understood. We recently developed an hESC-based model in which migratory cells undergo epithelial to mesenchymal transition (EMT) to acquire properties of neural crest (NC) cells. In this model, we found that migratory NC progenitors downregulate SOX2, but then start re-expressing SOX2 as they differentiate to form neurogenic dorsal root ganglion (DRG)-like clusters. SOX2 downregulation was sufficient to induce EMT and resulted in massive apoptosis when neuronal differentiation was induced. In vivo, downregulation of SOX2 in chick and mouse NC cells significantly reduced the numbers of neurons within DRG. We found that SOX2 binds directly to NGN1 and MASH1 promoters and is required for their expression. Our data suggest that SOX2 plays a key role for NGN1-dependent acquisition of neuronal fates in sensory ganglia.

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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 2011 Elsevier Inc. Received 16 July 2010; revised 26 January 2011; accepted 4 March 2011. Published: May 5, 2011. Available online 5 May 2011. We thank C.-T. Huang and K. Liu for their help with cloning, lentiviral production, and microarray analysis. We thank Dr. S. Albini, Dr. S. Forcales, and Professor L. Puri for sharing their expertise in chromatin immunoprecipitation techniques. Sox2LoxP mice were kindly provided by Dr. Nicolis, and Wnt1-CRE mice were kindly provided by Dr. Y. Yamaguchi. We thank Dr. J. Hou for helping with IP-MS data analysis. This work has been supported by CIRM postdoctoral fellowship to F.C., CIRM grant RS1004661 to A.T., and transient research support to A.V. Terskikh from the Sanford-Burnham Medical Research Institute and an NIH Blueprint core grant (PI, S.A. Lipton).
Funding AgencyGrant Number
California Institute for Regenerative Medicine (CIRM)RS1004661
Sanford-Burnham Medical Research InstituteUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC4110917
Record Number:CaltechAUTHORS:20110614-133159726
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Official Citation:Flavio Cimadamore, Katherine Fishwick, Elena Giusto, Ksenia Gnedeva, Giulio Cattarossi, Amber Miller, Stefano Pluchino, Laurence M. Brill, Marianne Bronner-Fraser, Alexey V. Terskikh, Human ESC-Derived Neural Crest Model Reveals a Key Role for SOX2 in Sensory Neurogenesis, Cell Stem Cell, Volume 8, Issue 5, 6 May 2011, Pages 538-551, ISSN 1934-5909, DOI: 10.1016/j.stem.2011.03.011. (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24005
Deposited By: Ruth Sustaita
Deposited On:14 Jun 2011 21:17
Last Modified:03 Oct 2019 02:52

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