Late neural progenitors hinge on Sox9 for cell fate determination in mouse spinal cord

BERTI JOSELINA; CAMPETELLA CARLA AGUSTINA; LANUZA GUILLERMO MARCOS

Ribeirão Preto

Congreso; ISSCR 2023 São Paulo International Symposium Hybrid Meeting; 2023

International Society for Stem Cell Research (ISSCR)

Neural progenitors give rise to both neurons and glial cells during distinct stages of central nervous system development. Therefore, their transcriptional programs must be altered in order to generate such different cell types. Among the many mechanisms involved in the neuro-to-glial switch lies Sox9 expression, necessary for glial specification. Even though the separate timing of neuro and gliogenesis was a well-established principle, the mouse spinal cord cerebrospinal fluid-contacting neurons (CSF-cNs) are an exception. These peculiar neurons arise at late developmental stages along with astrocytes, oligodendrocytes, and ependimocytes. In this work, we demonstrate that the lack of Sox9 leads to an increased production of neurons expressing the ion channel Pkd2l1, characteristic of CSF-cNs. These cells follow the classical differentiation program of CSF-cNs, initiated by the proneural protein Ascl1 and continued by the Gata3/2 transcription factors in their postmitotic specification. We show that neuronal overproduction in mutants originates from the p2/pOL progenitor domain. We also suggest that the change in potency of neural progenitors is delayed, leading to improper timing of glial development, shown by a reduction of Nfia+;Sox2+ cells. Altogether, our results demonstrate that Sox9 promotes progenitor determination towards glial fates, and its absence triggers differentiation of CSF-cNs during late spinal cord development.