Descripción del proyecto
Dilucidar la formación de neuronas en el encéfalo
Se cree que el proceso de formación de nuevas neuronas en el encéfalo —conocido como neurogénesis— se produce a lo largo de toda la vida en regiones específicas. Sin embargo, hay muchos aspectos que siguen sin conocerse bien. El equipo proyecto EDeN, financiado por el Consejo Europeo de Investigación, estudiará el papel del nicho neurogénico y, en particular, el apoyo prestado por los ependimócitos. Estas células tienen un origen epitelial y desempeñan un papel crucial en el flujo del líquido cefalorraquídeo y la migración de nuevas neuronas. Los investigadores pretenden analizar los procesos celulares y moleculares implicados en el desarrollo y la diferenciación de los ependimócitos. Los resultados de esta investigación podrían conducir al descubrimiento de nuevas dianas terapéuticas para trastornos neurológicos graves.
Objetivo
Understanding how billions of neurons are born, migrate and integrate into functional circuits has proved useful in elucidating the pathomechanisms of many neurodevelopmental disorders. Multiciliated ependymal cells have attracted less interest and their development is still enigmatic. However, their strategic location at the interface between brain ventricles and parenchyma and their unique morphology and functions strongly suggest that defects in the generation of these cells may be associated with a variety of severe neurological disorders.
Multiciliated ependymal cells are epithelial cells that line all brain ventricles. The coordinated and oriented beating of their cilia is crucial for the flow of cerebrospinal fluid through the ventricles and the migration of new neurons. These cells also provide physical and trophic support that creates a permissive neurogenic environment in the adult.
We have shown that elongated bipolar radial glial cells transform into ependymal cells at late embryonic stages through mechanisms that remain largely to be explored. The overall objective of this grant application is to develop a new line of research to understand the cellular and molecular mechanisms involved in ependymal cell development. We will use a multidisciplinary approach involving mouse molecular genetics, biophysical approaches, ex-vivo culture systems and advanced live cell imaging to investigate: i) the mechanisms that direct the transformation of RGC into ependymal cells; ii) the mechanisms of centriole amplification in ependymal cell progenitors; iii) how developing ependymal cells contribute to ventricular morphogenesis and adult neurogenesis. This ambitious project will pave the way for the identification of new therapeutic targets for a variety of neurological disorders.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
75654 Paris
Francia