Borello Ugo, Berarducci Barbara, Delahaye Edwige, Price David J, Dehay Colette
Université de Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, Bron, France.
Inovarion, Paris, France.
Front Neurosci. 2018 Mar 2;12:119. doi: 10.3389/fnins.2018.00119. eCollection 2018.
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 () during the early developmental stages of the mouse cerebral cortex. We found evidence that SP8 binds to the locus on exon regions. experiments show SP8 binding activity on gene 3'-end, and point to a putative role for SP8 in modulating PAX6-mediated repression of along the dorso-ventral axis of the developing pallium, creating a medial-lateral gradient of neuronal differentiation. Activation of through the promoter/5'-end of the gene does not depend on SP8, but on βcatenin (CTNNB1). Importantly, alteration of the level of expression affects expression during early corticogenesis. Our results indicate that 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.
在皮质发生过程中，多种信号控制神经祖细胞增殖与分化之间的平衡。这种调控的一个关键点是对G1期长度的控制，其由细胞周期蛋白/周期蛋白依赖性激酶复合物调节。利用全基因组染色质免疫沉淀测定法和小鼠遗传学，我们探索了小鼠大脑皮质早期发育阶段（）的转录调控。我们发现有证据表明SP8结合到外显子区域的（）位点。实验表明SP8在（）基因3'端具有结合活性，并指出SP8在调节发育中的大脑皮层背腹轴上PAX6介导的（）抑制中具有推定作用，从而形成神经元分化的内外侧梯度。通过基因启动子/ 5'端激活（）不依赖于SP8，而是依赖于β连环蛋白（CTNNB1）。重要的是，（）表达水平的改变会影响皮质发生早期的（）表达。我们的结果表明，（）调控是多种信号作用的结果，并且SP8是这种调控中的一个参与者，揭示了一种意想不到的潜在新转录激活机制。
