The cerebral cortex contains an enormous number of neurons which underlies its ability to perform highly complex neural tasks. Understanding how these neurons develop at the correct time and place and in accurate numbers constitutes a major challenge. Here, we demonstrate a novel role for Gli3, a key regulator of cortical development, in cortical neurogenesis. We show that the onset of neuron formation is delayed in Gli3 conditional mutants. Gene expression profiling and cell cycle measurements indicated that shortening of the G1 and S phases in radial glial cells precedes this delay. Reduced G1 length correlates with an up-regulation of the cyclin dependent kinase Cdk6 which is directly regulated by Gli3. Moreover, pharmacological interference with Cdk6 function rescues the delayed neurogenesis in Gli3 mutant embryos. Overall, our data indicate that Gli3 controls the onset of cortical neurogenesis by determining the levels of Cdk6 expression thereby regulating neuronal output and cortical size.
Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression
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Kerstin Hasenpusch-Theil, Stephen West, Alexandra Kelman, Zrinko Kozic, Sophie Horrocks, Andrew P. McMahon, David J. Price, John O. Mason, Thomas Theil; Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression. Development 2018; dev.163147. doi: https://doi.org/10.1242/dev.163147
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