Role of reelin in cortical neurogenesis

Resumen

The reelin and Notch signaling pathways underlay key cellular mechanisms controlling vertebrate brain development. Reelin, whose function untill recently was believed to be exclusively on neuronal migration, has been now shown to be required for different cellular processes during development of the nervous system, from neural precursor cell morphogenesis to synaptogenesis. This multifunctional aspect of reelin is paralleled by Notch, with its specific role in the regulation of radial glia differentiation, neurogenic transition and control of neural differentiation. The cross-talk between the reelin and Notch signaling pathways during the migration of postmitotic cortical neurons in vivo, and the in vitro study of the reelin effect on human Neural Precursor Cell differentiation via Notch signaling have been two major contributions advancing the understanding of reelin function in brain development. Despite these advances there has not been a comprehensive study of reelin function on cortical neurogenesis. Such a study necessarily requires the analysis of both loss and gain-of-function conditions for reelin during embryonic cortical development. This work uses the classical genetic approach consisting on the developmental analysis of the null and the ectopic expression conditions for reelin during mouse embryonic cortical development in vivo and in vitro. Here we show the close relationship of reelin and Notch signaling pathways on neurogenesis and cell fate determination in the developing mouse brain. The results of this Thesis work show that reelin is a key modulator of Notch signaling during the transition from neuroepithelial growth to the neurogenic phase and a potent enhancer of Notch signaling during mouse cortical neurogenesis.