Dorà Elena, Price David J, Mason John O
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Front Cell Neurosci. 2019 Mar 6;13:78. doi: 10.3389/fncel.2019.00078. eCollection 2019.
The transcription factor Pax6 controls multiple aspects of forebrain development. Conditional deletion of in embryonic mouse cortex causes increased proliferation of cortical progenitor cells and a concomitant decrease in neural differentiation. Notch signaling regulates the balance between proliferation and differentiation of cortical progenitor cells, suggesting a possible connection between Pax6 and Notch signaling. We investigated how expression of the Notch ligand () is altered by loss of Pax6. Acute cortex-specific deletion of Pax6 resulted in a widespread decrease in the density of + cells at embryonic days 12.5 and 13.5 (E12.5 and E13.5). In constitutive loss-of-function mutants, decreases in the densities of + cells were more limited both spatially and temporally. Controlled over-expression of Pax6 had no detectable effect on expression. The proneural transcription factor Neurog2 is a target of Pax6 that can activate expression and we found clear co-expression of and in radial glial progenitors, suggesting that Pax6's effect on could be mediated through Neurog2. However, we found no change in + cells in cortex suggesting either that Neurog2 is not directly involved, or that its loss of function in embryonic cortex can be compensated for.
转录因子Pax6控制着前脑发育的多个方面。在胚胎小鼠皮质中条件性缺失Pax6会导致皮质祖细胞增殖增加，同时神经分化减少。Notch信号调节皮质祖细胞增殖与分化之间的平衡，这表明Pax6与Notch信号之间可能存在联系。我们研究了Pax6缺失如何改变Notch配体Delta-like 1（Dll1）的表达。在胚胎第12.5天和13.5天（E12.5和E13.5），急性皮质特异性缺失Pax6导致Dll1+细胞密度普遍降低。在组成型功能缺失突变体中，Dll1+细胞密度的降低在空间和时间上都更为有限。Pax6的可控过表达对Dll1表达没有可检测到的影响。神经源性转录因子Neurog2是Pax6的一个靶点，它可以激活Dll1表达，并且我们发现Dll1和Neurog2在放射状胶质祖细胞中有明显的共表达，这表明Pax6对Dll1的影响可能是通过Neurog2介导的。然而，我们发现在Neurog2缺失的皮质中Dll1+细胞没有变化，这表明要么Neurog2不直接参与，要么其在胚胎皮质中的功能丧失可以得到补偿。
