Abstract
Proneural transcription factors (TFs) such as Ascl1 function as master regulators of neurogenesis in vertebrates, being both necessary and sufficient for the activation of a full program of neuronal differentiation. Novel insights into the dynamics of Ascl1 expression at the cellular level, combined with the progressive characterization of its transcriptional program, have expanded the classical view of Ascl1 as a differentiation factor in neurogenesis. These advances resulted in a new model, whereby Ascl1 promotes sequentially the proliferation and differentiation of neural/stem progenitor cells. The multiple activities of Ascl1 are associated with the activation of distinct direct targets at progressive stages along the neuronal lineage. How this temporal pattern is established is poorly understood. Two modes of Ascl1 expression recently described (oscillatory vs. sustained) are likely to be of importance, together with additional mechanistic determinants such as the chromatin landscape and other transcriptional pathways. Here we revise these latest findings, and discuss their implications to the gene regulatory functions of Ascl1 during neurogenesis.
Highlights
Neurogenesis in the developing mammalian brain is a highly complex process that requires neural progenitor cells to progress through a succession of distinct cellular states
Radial glial (RG) cells in the ventricular zone (VZ) have characteristic features of neural stem/progenitor cells, as they self-renew by asymmetric division and have the potential to differentiate into both neurons and glial cells (Götz and Huttner, 2005)
Most RG cells divide at the apical surface of the VZ, while most intermediate progenitors divide more basally in the sub-ventricular zone (SVZ)
Summary
Transcriptional control of vertebrate neurogenesis by the proneural factor Ascl. Reviewed by: Joao R. Novel insights into the dynamics of Ascl expression at the cellular level, combined with the progressive characterization of its transcriptional program, have expanded the classical view of Ascl as a differentiation factor in neurogenesis. These advances resulted in a new model, whereby Ascl promotes sequentially the proliferation and differentiation of neural/stem progenitor cells. Two modes of Ascl expression recently described (oscillatory vs sustained) are likely to be of importance, together with additional mechanistic determinants such as the chromatin landscape and other transcriptional pathways We revise these latest findings, and discuss their implications to the gene regulatory functions of Ascl during neurogenesis
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