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Coordination of neuron production in mouse and human cerebral cortex by the homolog of Drosophila Mastermind protein

ABSTRACT: The coordination of progenitor self-renewal, neuronal production and migration is essential to the normal development and evolution of the cerebral cortex. Numerous studies have shown that the Notch, Wnt/beta-catenin and Neurogenin pathways contribute separately to progenitor expansion, neurogenesis, and neuronal migration, but it is unknown how these signals are coordinated. In vitro studies suggested that the mastermind-like 1 (MAML1) gene, homologue of the Drosophila Mastermind, plays a role in coordinating the afore-mentioned signaling pathways, yet its role during cortical development remains largely unknown. Here we show that ectopic expression of dominant-negative MAML (dnMAML) causes exuberant neuronal production in the mouse cortex without disrupting neuronal migration. Comparing the transcriptional consequences of dnMAML and Neurog2 ectopic expression revealed a complex genetic network controlling the balance of progenitor expansion versus neuronal production. Manilpulation of MAML and Neurog2 in cultured human cerebral stem cells exposed interactions with the same set of signaling pathways. Thus, our data suggest that evolutionary changes that affect the timing, tempo and density of successive neuronal layers of the small lissencephalic rodent and large convoluted primate cerebral cortex depend on similar molecular mechanisms that act from the earliest developmental stages.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE76491 | GEO | 2019/09/09

REPOSITORIES: GEO

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Proneural genes define ground state rules to regulate neurogenic patterning and cortical folding

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