Transcriptional control of late neuronal specification in the developing mouse spinal cord

DI BELLA, D.; CAMPETELLA, C; LANUZA, G.; CARCAGNO, A.

Buenos Aires

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

LASDB, Latin American Society for Developmental Biology

During advanced phases of embryonic development, after the neurogenic-to-gliogenic switch, some spinal cord progenitors have the capacity to produce neurons. We have shown that late neurogenesis exclusively produces CerebroSpinal Fluid-contacting Neurons (CSF-cNs), a discrete neuron type of the ependymal area (1), whose development is triggered by Ascl1 (2). Here we show that differentiating CSF-cNs express the transcription factors Gata3 and Gata2, downstream of Ascl1. With lineage tracing of Ascl1+ cells, we analyzed the temporal activation of Gata3/2 and found that while Gata3 is expressed transiently, Gata2 maintains in CSF-cNs even postnatally. To determine the role of Gata3/2 in CSF-cN specification, we generated Gata3 conditional knockouts and found that Gata2 fails to be induced in the dorsal subset of CSF-cNs (CSF-cNs?) but its activation in CSF-CNs? (the ventral cluster) is independent of Gata3. At perinatal stages Gata3-cKOs lack of CSF-cNs? (assessed by Pkd2l1, the marker of central canal neurons), while CSF-cNs? are preserved. We also generated Gata3/2 double conditional mutants, and found a complete absence of CSF-cNs in their spinal cord central canal. These results suggest that Gata2 is able to compensate the absence of Gata3 during CSF-cN? differentiation, and, most significantly, that global Gata3/2 activity is essential for the postmitotic specification of both CSF-cN subclasses