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Publication : Cell Type-Specific Transcriptional Control of Gsk3β in the Developing Mammalian Neocortex.

First Author  Nomura T Year  2022
Journal  Front Neurosci Volume  16
Pages  811689 PubMed ID  35401100
Mgi Jnum  J:323188 Mgi Id  MGI:7261901
Doi  10.3389/fnins.2022.811689 Citation  Nomura T, et al. (2022) Cell Type-Specific Transcriptional Control of Gsk3beta in the Developing Mammalian Neocortex. Front Neurosci 16:811689
abstractText  Temporal control of neurogenesis is central for the development and evolution of species-specific brain architectures. The balance between progenitor expansion and neuronal differentiation is tightly coordinated by cell-intrinsic and cell-extrinsic cues. Wnt signaling plays pivotal roles in the proliferation and differentiation of neural progenitors in a temporal manner. However, regulatory mechanisms that adjust intracellular signaling amplitudes according to cell fate progression remain to be elucidated. Here, we report the transcriptional controls of Gsk3beta, a critical regulator of Wnt signaling, in the developing mouse neocortex. Gsk3beta expression was higher in ventricular neural progenitors, while it gradually declined in differentiated neurons. We identified active cis-regulatory module (CRM) of Gsk3beta that responded to cell type-specific transcription factors, such as Sox2, Sox9, and Neurogenin2. Furthermore, we found extensive conservation of the CRM among mammals but not in non-mammalian amniotes. Our data suggest that a mammalian-specific CRM drives the cell type-specific activity of Gsk3beta to fine tune Wnt signaling, which contributes to the tight control of neurogenesis during neocortical development.
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