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

Abstract

Functionally distinct classes of dorsal root ganglia (DRG) somatosensory neurons arise from neural crest cells (NCCs) during two successive phases of differentiation assumed to be respectively controlled by the proneural genes Neurog2 and Neurog1. However, the individual requirement of Neurog2 in this system still remains unclear notably since no neuronal loss has been reported hitherto in Neurog2^-/- mutants. Here, we reveal that at thoracic levels, Neurog2-deficiency generally impairs the formation of subsets of all somatosensory neuron subtypes. We establish that this phenotype is highly dynamic and reflects multiple defects in NCCs, 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 Neurog1 induction and onset of neurogenesis. Collectively, these findings uncover a critical period of cell fate plasticity and vulnerability for NCC-derived somatosensory progenitors and establish that Neurog2 function in the developing DRG is broader than initially predicted.

Keywords: cell fate specification, dorsal root ganglion, lineage commitment, melanocyte, neural crest cells, Neurog1, Neurog2, neurogenesis, Peripheral somatosensory system, somatosensory neurons