Article

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

Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell stem cell (Impact Factor: 22.27). 05/2011; 8(5):538-51. DOI: 10.1016/j.stem.2011.03.011
Source: PubMed

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.

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Available from: Flavio Cimadamore
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    • "SOX10 and FOXD3 are strongly expressed by premigratory neural crest (Figure 1A) and associated with maintenance of multipotency (Kim et al., 2003, 2014; Nitzan et al., 2013; Teng et al., 2008). In contrast, neural stem cell marker SOX2 is downregulated in dorsal relative to ventral neural tube regions (Figure 1A), albeit required at low levels for neural crest EMT (Cimadamore et al., 2011). Transcript levels were compared with those in whole embryo lysates using qPCR (see the Supplemental Results; Figure S1A). "
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    • "During the developmental stage of peripheral nervous system (PNS), Sox2 is expressed in neural crest stem cells and regulates the differentiation to DRG neurons [9] [10]. Sox2 is also expressed in immature Schwann cells and inhibits myelination [11]. "
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    • "Similar to other vertebrate species, like chick, mouse and human, SOX2 labels pre-migratory NC cells of the dorsal neural epithelium. Its expression is down-regulated in migrating neural crest cells, and turned back on in neuronal progenitors of sensory ganglia (Cimadamore et al., 2011). However, although unlikely, we should still consider the possibility that in the axolotl, SOX2 is labeling a different cell population compared to reports for other species. "
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