Sox9 regulates the choice between glial and late neuronal fates in the developing spinal cord

BERTI JOSELINA; CAMPETELLA CARLA AGUSTINA; LANUZA GUILLERMO MARCOS

Chascomús

Congreso; V Taller de Biología Celular y del Desarrollo; 2022

Neurons and glial cells are sequentially produced during embryonic development, and this temporal order is conserved in all species and regions of the nervous system. Neurogenic events have been considered to be completed by the time the gliogenesis begins. However, the spinal cord cerebrospinal fluid-contacting neurons (CSF-cNs) are an exception to this general principle, being generated at late stages together with astrocytes, oligodendrocytes and ependymocytes. The precise molecular mechanisms that determine the equilibrium between these distinct cell types are unknown. In this work, we show that the transcription factor Sox9 regulates the glial vs. neuronal fate choice balance. We found that Sox9 conditional mutants have an expanded production of spinal CSF-cNs. This increase is accompanied by impaired astrocyte differentiation, revealed by a reduced number of Sox2+,Nfia+ cells in the mantle zone, and lower GFAP immunoreactivity. Moreover, we show that the respecification towards CSF-cN follows a differentiation program initiated by the proneural protein Ascl1 and continued by the postmitotic transcription factors Gata3/2. Altogether, our results demonstrate that Sox9 promotes glial cell fate determination, as its absence leads to failure in astrocytic commitment thus triggering CSF-cN differentiation.