title: Human ESC-derived neural crest model reveals a key role for SOX2 in sensory neurogenesis.
abstract: 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.
authors.affiliation: Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. flavioc@burnham.org
authors.forename: Flavio
authors.initials: F
authors.lastname: Cimadamore
authors.forename: Katherine
authors.initials: K
authors.lastname: Fishwick
authors.forename: Elena
authors.initials: E
authors.lastname: Giusto
authors.forename: Ksenia
authors.initials: K
authors.lastname: Gnedeva
authors.forename: Giulio
authors.initials: G
authors.lastname: Cattarossi
authors.forename: Amber
authors.initials: A
authors.lastname: Miller
authors.forename: Stefano
authors.initials: S
authors.lastname: Pluchino
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Brill
authors.forename: Marianne
authors.initials: M
authors.lastname: Bronner-Fraser
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Terskikh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement; D002645:Chickens; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology; D055495:Neurogenesis / Q000235:genetics; D009928:Organ Specificity; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; C065500:ASCL1 protein, human; C105389:NEUROG1 protein, human; C527782:SOX2 protein, human