Transcriptional control of the specification of spinal CSF-contacting neurons

MARIA BELÉN PARDI; ANTONIA MARIN-BURGIN; ABEL CARCAGNO; DANIELA DI BELLA; LUCIANO BRUM; MICAELA SARTORETTI; GUILLERMO LANUZA

San Diego

Congreso; Annual Meeting Society for Neuroscience 2016; 2016

The generation of precise neuronal types in the right time and quantity, is essential for building a functioning nervous system. In the last 20 years, we have reached a huge understanding of the genetic mechanisms that control neuron specification during embryonic development, in which extrinsic cues are translated into positional coordinates that determine neuronal identity. However, the temporal contribution to neuronal diversity has been less explored. We have recently identified a neurogenic event in the amniote spinal cord that takes place simultaneously with glial specification, during advanced developmental stages previously considered non-neurogenic. CerebroSpinal Fluid contacting Neurons (CSF-cN), widely conserved in chordates, are located at the interface between the central nervous system and the CSF and are generated from late ventral progenitors. The genetic mechanisms that allow the differentiation of this class of neurons at gliogenic stages are unknown. In this work, weidentified that the transcription factors Ascl1, Gata3 and Gata2 are sequentially expressed in mouse CSF-cN and control their specification. Through expression analysis and mouse genetics, we described that Gata3 and Gata2 are postmitotically expressed in CSF-cN, where they control the acquisition of this neuronal identity. Loss of function experiments showed that Gata3 and Gata2 play distinct roles in different CSF-cN subsets. Meanwhile, the proneural protein Ascl1 is expressed in late ventral proliferating progenitors that give rise to CSF-cN and is exclusively necessary for their differentiation in amniotes. By temporal dissection of Ascl1 activity, we found that this transcription factor is an essential component of late CSF-cN neurogenesis, acting at the time of their specification. 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 the sequencial action of Ascl1-Gata3/2 directs the late specification of CSF-cN in amniotes. Ascl1 acts governing the onset of neuronal differentiation in the gliogenic neural tube and Gata3/2 control CSF-cN identity.