CONICET | Buscador de Institutos y Recursos Humanos

In spite of the progress made in understanding early events in cell specification, the mechanisms that lead to the diversity of neuronal types remain to be elucidated. In the developing neural tube, distinct populations of neurons arise at specific dorso-ventral positions. In order to analyze how early embryonic population contribute to different cell types, we used Cre/loxp labeling systems to fate map descendents of V2b cells, one ventral group of embryonic neurons that express the transcription factors Gata2/3. By performing cell lineage tracing in the Gata3Cre and in the Gata2GFP mouse, we identified a novel population of cells in lamina X of the spinal cord, which is distinct to V2b-derived interneurons that locate in lamina VII. These cells, termed cerebrospinal fluid-contacting neurons (CCNs), have a unique morphology, with a dendritic-like process through the ependyma into the central canal. We found that CCNs are born from ventral progenitors at E13-14, when neurogenesis in the neural tube is almost completed. The late birthdate of CCNs contrasts with the earlier progenitor cell cycle exit that generates lamina VII Gata2/3 neurons. The genetic mechanisms that control the development of early-born V2b cells requires the activity of the transcription factor Foxn4 and Notch signaling pathway. On the other hand, the differentiation of CCNs appears normal in Foxn4-/- and in Presenilin1 mutant mice, indicating that different genetic mechanisms are involved in the genesis of distinct subsets of Gata2/3 spinal neurons. These results show that restricted populations of precursors in the developing tube can sequentially differentiate into separate neuronal subtypes, contributing to the diversification of neuronal fates.