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

SOX2 is a transcription factor with capital importance in central nervous system development and neural precursor cell (NPC) biology, which is witnessed by the severe phenotypes observed in humans with SOX2 mutations. SOX2 haploinsufficiency syndrome manifests in fact with absence of eyes, abnormal hippocampus development and intellectual deficits among others. However, little was known about the role of this gene in peripheral nervous system (PNS) development. NPCs of the peripheral nervous system arise from a developmental population of cells termed neural crest (NC). In this work we explored the role of SOX2 in NC cells and the genesis of peripheral sensory neurons. By using a combination of transgenic mice and human embryonic derived-NC cells to model the peripheral nervous system development we showed that, in post-migratory NC cells, SOX2 is re-expressed in sensory neuron precursor of the dorsal root ganglia and it acts in this type of NPCs as a pluripotency factor by conferring such cells the ability to become neurons. In the absence of SOX2, NPCs fail to respond to neurogenic cues, fail to up-regulate pro-neural genes required for neuronal differentiation and, ultimately, die. This is first report showing a critical role of SOX2 in peripheral nervous system development and might explain why SOX2 mutations in human have some pathological features in common with the neural crest-related pathology CHARGE, such as sensorineural deafness.