Neurog2 Deficiency Uncovers a Critical Period of Cell Fate Plasticity and Vulnerability among Neural-Crest-Derived Somatosensory Progenitors

• Main Authors: Stéphanie Ventéo, Simon Desiderio, Pauline Cabochette, Alexandre Deslys, Patrick Carroll, Alexandre Pattyn
• Format: Article
• Language: English
• Published: Elsevier 2019-12-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719314731

Summary: Functionally distinct classes of dorsal root ganglia (DRG) somatosensory neurons arise from neural crest cells (NCCs) in two successive phases of differentiation assumed to be respectively and independently controlled by the proneural genes Neurog2 and Neurog1. However, the precise role of Neurog2 during this process remains unclear, notably because no neuronal loss has been reported hitherto in Neurog2−/− mutants. Here, we show that at trunk levels, Neurog2 deficiency impairs the production of subsets of all DRG neuron subtypes. We establish that this phenotype is highly dynamic and reflects multiple defects in NCC-derived progenitors, including somatosensory-to-melanocyte fate switch, apoptosis, and delayed differentiation which alters neuronal identity, all occurring during a narrow time window when Neurog2 temporarily controls onset of Neurog1 expression and neurogenesis. Collectively, these findings uncover a critical period of cell fate plasticity and vulnerability among somatosensory progenitors and establish that Neurog2 function in the developing DRG is broader than initially envisaged. : Ventéo et al. report that in contrast to cervical levels, trunk dorsal root ganglia of Neurog2−/− mutants contain reduced numbers of all somatosensory neuron subtypes due to multiple defects in neural-crest-derived progenitors—including sensory-to-melanocyte fate switch, apoptosis, and delayed differentiation—that affect the accuracy of the successive waves of neurogenesis. Keywords: cell fate specification, dorsal root ganglion, lineage commitment, melanocyte, neural crest cells, Neurog1, Neurog2, neurogenesis, peripheral somatosensory system, somatosensory neurons