Open AccessGli3controls the onset of cortical neurogenesis by regulating the radial glial cell cycle throughCdk6expression
Author(s) -
Kerstin HasenpuschTheil,
Stephen C. West,
Alexandra Kelman,
Zrinko Kozić,
Sophie Horrocks,
Andrew P. McMahon,
David J. Price,
John O. Mason,
Thomas Theil
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.163147
Subject(s) - neurogenesis , biology , cyclin dependent kinase 6 , gli3 , neuroscience , downregulation and upregulation , cell cycle , microbiology and biotechnology , cortex (anatomy) , cerebral cortex , cyclin , gene expression , cell , genetics , gene , repressor
The cerebral cortex contains an enormous number of neurons, allowing it 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 mouse mutants. Gene expression profiling and cell cycle measurements indicate that shortening of the G1 and S phases in radial glial cells precedes this delay. Reduced G1 length correlates with an upregulation of the cyclin-dependent kinase gene 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.