Delgado Ryan N, Lim Daniel A
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA,, United States.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA,, United States.
Front Mol Neurosci. 2017 Nov 13;10:373. doi: 10.3389/fnmol.2017.00373. eCollection 2017.
Throughout embryonic development and into postnatal life, regionally distinct populations of neural progenitor cells (NPCs) collectively generate the many different types of neurons that underlie the complex structure and function of the adult mammalian brain. At very early stages of telencephalic development, NPCs become organized into regional domains that each produce different subsets of neurons. This positional identity of NPCs relates to the regional expression of specific, fate-determining homeodomain transcription factors. As development progresses, the brain undergoes vast changes in both size and shape, yet important aspects of NPC positional identity persist even into the postnatal brain. How can NPC positional identity, which is established so early in brain development, endure the many dynamic, large-scale and complex changes that occur over a relatively long period of time? In this Perspective article, we review data and concepts derived from studies in regarding the function of homeobox (Hox) genes, Polycomb group (PcG) and trithorax group (trxG) chromatin regulators. We then discuss how this knowledge may contribute to our understanding of the maintenance of positional identity of NPCs in the mammalian telencephalon. Similar to the axial body plan of larvae, there is a segmental nature to NPC positional identity, with loss of specific homeodomain transcription factors causing homeotic-like shifts in brain development. Finally, we speculate about the role of mammalian PcG and trxG factors in the long-term maintenance of NPC positional identity and certain neurodevelopmental disorders.
在整个胚胎发育过程以及出生后的生命阶段，神经祖细胞（NPCs）的区域特异性群体共同产生了构成成年哺乳动物大脑复杂结构和功能基础的多种不同类型的神经元。在端脑发育的早期阶段，NPCs 会组织成不同的区域，每个区域产生不同的神经元亚群。NPCs 的这种位置身份与特定的、决定命运的同源域转录因子的区域表达有关。随着发育的进行，大脑在大小和形状上都会发生巨大变化，但 NPC 位置身份的重要方面甚至在出生后的大脑中仍然持续存在。在大脑发育早期就已确立的 NPC 位置身份，如何能经受住相对较长时期内发生的众多动态、大规模和复杂的变化呢？在这篇观点文章中，我们回顾了来自有关同源框（Hox）基因、多梳蛋白组（PcG）和三胸蛋白组（trxG）染色质调节因子功能研究的数据和概念。然后我们讨论这些知识如何有助于我们理解哺乳动物端脑中 NPC 位置身份的维持。与果蝇幼虫的轴向身体模式类似，NPC 位置身份具有分段性质，特定同源域转录因子的缺失会导致大脑发育中出现类似同源异型的转变。最后，我们推测哺乳动物 PcG 和 trxG 因子在 NPC 位置身份的长期维持以及某些神经发育障碍中的作用。
