Ascl1 confers neurogenic potential to late progenitors of the mouse spinal cord

DI BELLA, D.; PARDI, MB; BARTOLOMEU, L.; MARIN BURGIN, A; CARCAGNO, A.; SIEGEL, N.; LANUZA, G.

Buenos aires

Congreso; Latin American Society for Developmental Biology Meeting 2019; 2019

LASDB, Latin American Society for Developmental Biology

The generation of the precise neuronal types at the right time, location and number, is essential for building a functional nervous system. In the last 20 years, considerable progress has been made in understanding the genetic mechanisms that control neuron specification during embryonic development, and how positional coordinates determine neuronal identity. However, the temporal contribution to neuronal diversity has been less explored. We have recently identified a neurogenic event in the mouse spinal cord that takes place, during advanced embryonic stages, simultaneously with glial specification previously considered non-neurogenic. CerebroSpinal Fluid contacting Neurons (CSF cN) are widely conserved in chordates, have a unique morphology and are generated from late ventral spinal cord progenitors. The genetic mechanisms that allow the differentiation of this class of neurons at gliogenic stages are unknown. Using knock-out mice, genetic labeling and expression analysis we show that the transcription factor Ascl1 is expressed in progenitors that give rise to CSF cN and that Ascl1 is necessary for CSF-cN development. Finally, fate mapping experiments in the absence of Ascl1 demonstrated that it confers neurogenic potential to late ventral progenitors, which would otherwise become ependymal cells. We conclude that Ascl1 directs the specification of CSF cN in the gliogenic neural tube controlling the precise neuronal and nonneuronal composition of the spinal central canal.