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Topographic signaling and spatial landmarks of key polarized neuro-developmental processes

Final Report Summary - YODA (Topographic signaling and spatial landmarks of key polarized neuro-developmental processes)

Our project addresses the fascinating question of how cells acquire precise spatial orientation in their tissue during the development of the nervous system. We explored the nature of the spatial landmarks provided to the cells during two key developmental steps, the division of neural progenitors giving rise to neurons, and the acquisition of specialized morphologies by new-born neurons. First, we uncovered that molecular cues are released in the cerebrospinal fluid at earlier stages in the embryo. These cues are collected by progenitors and regulate the orientation of their division in the neuroepithelium. We identified one such molecule, which belongs to a vast family of proteins known to participate to the formation of neuronal connections, the Semaphorins. Second we uncovered the existence of a mechanism which allows the transmission of cell morphologies from progenitors to their daughter neurons. The initial shape of the progenitor is stored by a molecular system during the steps when progenitors must change their morphology to divide, and is restituted in the daughter neurons generated by the division. This mechanism allows the transmission of specific cell shape over the generations. We identified the Septins, forming a molecular network known in the yeast to position the budding site, as central players of this molecular memory.