Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced, Merced, CA 95340, USA.
Cells. 2023 Dec 21;13(1):21. doi: 10.3390/cells13010021.
The Hedgehog (Hh) pathway plays a crucial role in embryonic development, acting both as a morphogenic signal that organizes tissue formation and a potent mitogenic signal driving cell proliferation. Dysregulated Hh signaling leads to various developmental defects in the brain. This article aims to review the roles of Hh signaling in the development of the neocortex in the mammalian brain, focusing on its regulation of neural progenitor proliferation and neuronal production. The review will summarize studies on genetic mouse models that have targeted different components of the Hh pathway, such as the ligand Shh, the receptor Ptch1, the GPCR-like transducer Smo, the intracellular transducer Sufu, and the three Gli transcription factors. As key insights into the Hh signaling transduction mechanism were obtained from mouse models displaying neural tube defects, this review will also cover some studies on Hh signaling in neural tube development. The results from these genetic mouse models suggest an intriguing hypothesis that elevated Hh signaling may play a role in the gyrification of the brain in certain species. Additionally, the distinctive production of GABAergic interneurons in the dorsal cortex in the human brain may also be linked to the extension of Hh signaling from the ventral to the dorsal brain region. Overall, these results suggest key roles of Hh signaling as both a morphogenic and mitogenic signal during the forebrain development and imply the potential involvement of Hh signaling in the evolutionary expansion of the neocortex.
Hedgehog (Hh) 信号通路在胚胎发育中起着至关重要的作用，它既是组织形成的形态发生信号，也是驱动细胞增殖的有力有丝分裂信号。Hh 信号通路的失调会导致大脑出现各种发育缺陷。本文旨在综述 Hh 信号通路在哺乳动物大脑新皮层发育中的作用，重点关注其对神经祖细胞增殖和神经元产生的调节作用。该综述将总结针对 Hh 通路不同成分（如配体 Shh、受体 Ptch1、GPCR 样转导 Smo、细胞内转导 Sufu 和三个 Gli 转录因子）的遗传小鼠模型的研究。由于从显示神经管缺陷的小鼠模型中获得了对 Hh 信号转导机制的关键见解，本综述还将涵盖一些关于 Hh 信号在神经管发育中的研究。这些遗传小鼠模型的结果提出了一个有趣的假设，即升高的 Hh 信号可能在某些物种的大脑脑回形成中起作用。此外，人类大脑背侧皮质中 GABA 能中间神经元的独特产生也可能与 Hh 信号从腹侧向背侧脑区的延伸有关。总之，这些结果表明 Hh 信号在大脑前脑发育中既是形态发生信号又是有丝分裂信号，并暗示 Hh 信号可能参与了新皮层的进化扩展。
