Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor.
Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor.
复制标题
DOI：
10.3389/fncel.2015.00070
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Price DJ
中科院分区：
文献类型：
--
作者：
Manuel MN;Mi D;Mason JO;Price DJ
理解大脑发育仍然是理解人类本质的一个主要挑战。从进化的角度来看，新皮层是大脑皮层的最新部分，是高级认知功能的所在地。它的正常发育需要大量兴奋性和抑制性神经元的产生、定位和适当的连接。Pax6是一组相对较小的转录因子之一，对皮质发育起高度控制作用，其在发育胚胎中的突变或缺失会导致严重的脑缺陷和广泛的神经发育障碍。Pax6在灵长类动物和非灵长类动物之间高度保守，在整个发育中的皮质中呈梯度表达，对正常的皮质发生至关重要。在过去的十年中，由于遗传和生化分析的结合应用，我们对Pax6的功能及其在哺乳动物皮质发育过程中调节的细胞过程的理解有了显著的进展。在这里，我们回顾了Pax6在调节皮质祖细胞增殖、神经发生和皮质层形成中的功能重要性，并强调了啮齿动物和灵长类动物之间的重要差异。我们还回顾了PAX6突变在人类神经发育障碍中的病理作用。我们讨论了Pax6分子作用的一些方面，包括其自身复杂的转录调控，其剪接变体的独特分子功能以及Pax6在皮质发育过程中介导其作用的一些已知的直接靶点。
Understanding brain development remains a major challenge at the heart of understanding what makes us human. The neocortex, in evolutionary terms the newest part of the cerebral cortex, is the seat of higher cognitive functions. Its normal development requires the production, positioning, and appropriate interconnection of very large numbers of both excitatory and inhibitory neurons. Pax6 is one of a relatively small group of transcription factors that exert high-level control of cortical development, and whose mutation or deletion from developing embryos causes major brain defects and a wide range of neurodevelopmental disorders. Pax6 is very highly conserved between primate and non-primate species, is expressed in a gradient throughout the developing cortex and is essential for normal corticogenesis. Our understanding of Pax6’s functions and the cellular processes that it regulates during mammalian cortical development has significantly advanced in the last decade, owing to the combined application of genetic and biochemical analyses. Here, we review the functional importance of Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of cortical layers and highlight important differences between rodents and primates. We also review the pathological effects of PAX6 mutations in human neurodevelopmental disorders. We discuss some aspects of Pax6’s molecular actions including its own complex transcriptional regulation, the distinct molecular functions of its splice variants and some of Pax6’s known direct targets which mediate its actions during cortical development.
登录
查看更多内容
影响因子：
3.5
作者：
Azuma, N;Tadokoro, K;Nakafuku, M
通讯作者：
Nakafuku, M
影响因子：
3.7
作者：
Britz, Olivier;Mattar, Pierre;Schuurmans, Carol
通讯作者：
Schuurmans, Carol
影响因子：
5.3
作者：
CARRIERE, C;PLAZA, S;SAULE, S
通讯作者：
SAULE, S
影响因子：
4.6
作者：
Berger, Joachim;Berger, Silke;Stoykova, Anastassia
通讯作者：
Stoykova, Anastassia
影响因子：
2.7
作者：
Bamiou, Doris-Eva;Campbell, Nicole G.;Luxon, Linda M.
通讯作者：
Luxon, Linda M.