Ascl1 balances neuronal vs. ependymal fate in the spinal cord central canal.

DI BELLA DJ* CO-PRIMER AUTOR; CARCAGNO AL* CO-PRIMER AUTOR; BARTOLOMEU ML; PARDI MB; LÖHR H; SIEGEL N; HAMMERSCHMIDT M; MARIN-BURGUIN A; LANUZA GM

Cell Reports

Elsevier

Lugar: Amsterdam; Año: 2019 vol. 28 p. 2264 - 2274

2211-1247

The generation of neuronal cell types at the right time, location and number is essential for building a functional nervous system. Significant progress has been reached in understanding the genetic mechanisms that govern neuronal diversity. CerebroSpinal Fluid-contacting Neurons (CSF-cNs), an intriguing specialized population of the spinal cord central canal, are produced during advanced developmental stages, simultaneous with glial and ependymal cells. It is unknown how late-born CSF-cNs are specified and how progenitors acquire neuronal potential after the neurogenic-to-gliogenic switch. Here, we identified that delayed expression of the transcription factor Ascl1 in mouse spinal progenitors during the gliogenic phase is key in CSF-cN differentiation. With fate mappings and time-controlled deletions, we demonstrate that CSF-cNs derive from Ascl1-expressing cells and that Ascl1 triggers late neurogenesis in the amniote spinal cord. Abrogation of Ascl1 transforms prospective CSF-cN progenitors into ependymocytes. These results demonstrate that late spinal progenitors have the potential to produce neurons and that Ascl1 initiates CSF-cN differentiation, controlling the precise neuronal and non-neuronal composition of the spinal cord central canal.