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Front. Neurosci. | doi: 10.3389/fnins.2018.00119

SP8 transcriptional regulation of Cyclin D1 during mouse early corticogenesis

 Ugo Borello1, 2, 3, Barbara Berarducci1, 2, Edwige Delahaye1, 2,  David J. Price4 and  Colette Dehay1, 2*
  • 1Université Claude Bernard Lyon 1, Université de Lyon, France
  • 2INSERM U1208 Institut Cellule Souche et Cerveau, France
  • 3Inovarion, France
  • 4Centre for Integrative Physiology, University of Edinburgh, United Kingdom

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 Cyclin D1 (Ccnd1) during the early developmental stages of the mouse cerebral cortex. We found evidence that SP8 binds to the Ccnd1 locus, specifically on exon regions. In vitro experiments show a specific SP8 activity on Ccdn1 gene 3’-end, and point to a putative role for SP8 in modulating PAX6-mediated repression of Ccnd1 along the dorso-ventral axis of the developing pallium, creating a mediallow-lateralhigh gradient of neuronal differentiation. Activation of Ccnd1 through the promoter/5’-end of the gene does not depend on SP8, but on ßcatenin (CTNNB1). Importantly, alteration of the Sp8 level of expression in vivo affects Ccnd1 expression during early corticogenesis.
Our results indicate that Ccnd1 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.

Keywords: corticogenesis, Gene Expression Regulation, Cyclin D1, Transcription Factors, SP8, Pax6

Received: 03 Oct 2017; Accepted: 14 Feb 2018.

Edited by:

Wieland B Huttner, Max Planck Institute of Molecular Cell Biology and Genetics (MPG), Germany

Reviewed by:

Davide De Pietri Tonelli, Fondazione Istituto Italiano di Technologia, Italy
Victor Borrell, Consejo Superior de Investigaciones Científicas (CSIC), Spain  

Copyright: © 2018 Borello, Berarducci, Delahaye, Price and Dehay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Colette Dehay, Université de Lyon, Université Claude Bernard Lyon 1, Bron, France, colette.dehay@inserm.fr