OTX1 regulates cell cycle progression of neural progenitors in the developing cerebral cortex.

The progenitor cells in the cerebral cortex coordinate proliferation and mitotic exit to generate the correct number of neurons and glial cells during development. However, mechanisms for regulating the mitotic cycle of cortical progenitors are not fully understood. is one of the homeobox-containing transcription factors frequently implicated in the development of the central nervous system. Mice bearing a targeted deletion of exhibit brain hypoplasia and a decrease in the number of cortical neurons. We hypothesized that might be crucial to the proliferation and differentiation of cortical progenitors. knockdown by electroporation in the mouse brain reduced the proportion of the G phase while increasing the S and M phases of progenitor cells. The knockdown diminished Tbr1+ neurons but increased GFAP+ astrocytes in the early postnatal cortex as revealed by lineage tracing study. Tbr2+ basal progenitors lacking were held at the transit-amplifying stage. In contrast, overexpression of wildtype but not an astrocytoma-related mutant Y320C inhibited proliferation of the progenitor cells in embryonic cortex. This study demonstrates that is one of the key elements regulating cortical neurogenesis, and a loss-of-function in Otx1 may contribute to the overproduction of astrocytes .