On the dynamics of neurogenesis and cortical architecture

講演要旨

The size and function of tissues depend primarily on their cellular composition: number and types of cells. This is determined during development by the proliferative activity of stem cells, and the balance between their own self-renewal and the production of tissue-specialized cells. The cerebral cortex must contain the appropriate numbers of neurons in each layer to acquire its proper functional architecture, so neurogenesis must be precisely regulated along development. Cortical neurons are made either directly by Radial Glia Cells (RGCs) that self-consume, or indirectly from RGCs via Intermediate Progenitor Cells (IPCs), which largely preserves the RGC pool. According to the standing model, Direct Neurogenesis (DN) predominates at early stages of cortical development, progressively shifting to Indirect Neurogenesis (IDN) which predominates at late stages. However, this dynamics appears in conflict with the need for RGC self-renewal and amplification at early stages of neurogenesis, and their consumption at late stages.

I will present recent data from my laboratory, where we have studied the modes of neurogenesis along cortical development using multiple experimental approaches and computer simulation. Contrary to the established dogma, our data show that IDN predominates at early stages and gradually shifts to DN at late stages, by substantial remodeling of the RGC transcriptome. Genetic challenging of this dynamics results in deficient cortical architecture and microcephaly, as also predicted by our simulations.

These findings challenge the current model of cortical neurogenesis and prompt the re-interpretation of long-standing observations on the molecular mechanisms regulating this process, as well as its evolution.