Miller Alexander, Dasen Jeremy S
NYU Neuroscience Institute and Developmental Genetics Programs, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
Semin Cell Dev Biol. 2024 Jan-Feb;152-153:44-57. doi: 10.1016/j.semcdb.2023.03.014. Epub 2023 Apr 5.
The chromosomally-arrayed Hox gene family plays central roles in embryonic patterning and the specification of cell identities throughout the animal kingdom. In vertebrates, the relatively large number of Hox genes and pervasive expression throughout the body has hindered understanding of their biological roles during differentiation. Studies on the subtype diversification of spinal motor neurons (MNs) have provided a tractable system to explore the function of Hox genes during differentiation, and have provided an entry point to explore how neuronal fate determinants contribute to motor circuit assembly. Recent work, using both in vitro and in vivo models of MN subtype differentiation, have revealed how patterning morphogens and regulation of chromatin structure determine cell-type specific programs of gene expression. These studies have not only shed light on basic mechanisms of rostrocaudal patterning in vertebrates, but also have illuminated mechanistic principles of gene regulation that likely operate in the development and maintenance of terminal fates in other systems.
染色体排列的Hox基因家族在整个动物界的胚胎模式形成和细胞身份特化过程中发挥着核心作用。在脊椎动物中,相对大量的Hox基因以及在全身的广泛表达阻碍了人们对其在分化过程中生物学作用的理解。对脊髓运动神经元(MNs)亚型多样化的研究提供了一个易于处理的系统,以探索Hox基因在分化过程中的功能,并为探索神经元命运决定因素如何促进运动回路组装提供了一个切入点。最近的研究工作,利用MN亚型分化的体外和体内模型,揭示了模式形态发生素和染色质结构调节如何决定细胞类型特异性的基因表达程序。这些研究不仅阐明了脊椎动物前后模式形成的基本机制,还揭示了可能在其他系统的终末命运的发育和维持中起作用的基因调控机制原理。