Department of Pediatrics, Dell Pediatric Research Institute, The University of Texas at Austin/Dell Medical School, Austin, TX 78723, USA.
Ngenes Inc., Suwon 15495, South Korea.
Development. 2024 Oct 1;151(19). doi: 10.1242/dev.202705. Epub 2024 Oct 4.
Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be genetically epistatic to Gpr161 with respect to regulation of Shh signaling in mouse neural tube development. The Fuz protein biochemically interacts with Gpr161, and Fuz regulates Gpr161-mediated ciliary localization, a process that might utilize β-arrestin 2. Our study characterizes a previously unappreciated Gpr161-Fuz axis that regulates Shh signaling during mouse neural tube development.
声波刺猬（Shh）信号利用初级纤毛（细胞的天线）调节胚胎形态发生，初级纤毛充当信号枢纽。平面细胞极性信号的效应物 Fuz 通过促进纤毛形成来调节 Shh 信号，G 蛋白偶联受体 161（Gpr161）是 Shh 信号的负调节剂。携带编码这些蛋白质的基因之一发生突变的小鼠中观察到的表型畸形范围相似；然而，它们的功能关系尚未被探索。本研究鉴定了 Fuz 和 Gpr161 在小鼠神经管发育中的遗传和生化联系。发现 Fuz 在调节小鼠神经管发育中的 Shh 信号方面在遗传上与 Gpr161 上位性。Fuz 蛋白在生化上与 Gpr161 相互作用，并且 Fuz 调节 Gpr161 介导的纤毛定位，该过程可能利用β-arrestin 2。我们的研究描述了一个以前未被重视的 Gpr161-Fuz 轴，它在小鼠神经管发育过程中调节 Shh 信号。
