SOX10 determines glial fate choice in the dorsal root ganglia through destabilisation of neurogenic 2

Abstract

SOX10 is a key transcription factor that determines bipotent neural crest (NC) progenitors to acquire glial cell identity instead of sensory neurons in the dorsal root ganglia (DRG) but the underlying mechanisms are poorly understood. Here, we show that the initial overlapping expression of SOX10 and neurogenic determinant, Neurogenin 2 (NGN2) in avian bipotential trunk NC progenitors gradually segregate during migration towards the forming DRG. Overexpression of SOX10 results in destabilization of NGN2 protein through ubiquitination. Transcription profiling of SOX10 overexpressing cells identifies F-box only protein (FBXO9) as a SCF (Skp-Cul-F-box)-type ubiquitin ligase of NGN2. Overexpression of FBXO9 decreases NGN2 protein expression and promotes glial lineage differentiation, whereas opposite phenomenon was observed in FBXO9 knockdown cells. Inhibition of FBXO9 function in SOX10 overexpressing cells restores both NGN2 protein expression and sensory neurogenesis. Altogether, these results demonstrate that SOX10 induces FBXO9 to degrade NGN2 for promoting glial lineage differentiation in the DRG.