AUTHOR=Borello Ugo , Berarducci Barbara , Delahaye Edwige , Price David J. , Dehay Colette 

TITLE=SP8 Transcriptional Regulation of Cyclin D1 During Mouse Early Corticogenesis

JOURNAL=Frontiers in Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00119

DOI=10.3389/fnins.2018.00119

ISSN=1662-453X

ABSTRACT=<p>Multiple signals control the balance between proliferation and differentiation of neural progenitor cells during corticogenesis. A key point of this regulation is the control of G1 phase length, which is regulated by the Cyclin/Cdks complexes. Using genome-wide chromatin immunoprecipitation assay and mouse genetics, we have explored the transcriptional regulation of <italic>Cyclin D1</italic> (<italic>Ccnd1</italic>) during the early developmental stages of the mouse cerebral cortex. We found evidence that SP8 binds to the <italic>Ccnd1</italic> locus on exon regions. <italic>In vitro</italic> experiments show SP8 binding activity on <italic>Ccnd1</italic> gene 3′-end, and point to a putative role for SP8 in modulating PAX6-mediated repression of <italic>Ccnd1</italic> along the dorso-ventral axis of the developing pallium, creating a medial<sup>Low</sup>-lateral<sup>High</sup> gradient of neuronal differentiation. Activation of <italic>Ccnd1</italic> through the promoter/5′-end of the gene does not depend on SP8, but on βcatenin (CTNNB1). Importantly, alteration of the <italic>Sp8</italic> level of expression <italic>in vivo</italic> affects <italic>Ccnd1</italic> expression during early corticogenesis. Our results indicate that <italic>Ccnd1</italic> regulation is the result of multiple signals and that SP8 is a player in this regulation, revealing an unexpected and potentially novel mechanism of transcriptional activation.</p>