Department of Molecular, Cellular and Development Biology, University of Colorado, Boulder, Colorado, USA.
Molecular Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Genesis. 2024 Jun;62(3):e23602. doi: 10.1002/dvg.23602.
Cilia play a key role in the regulation of signaling pathways required for embryonic development, including the proper formation of the neural tube, the precursor to the brain and spinal cord. Forward genetic screens were used to generate mouse lines that display neural tube defects (NTD) and secondary phenotypes useful in interrogating function. We describe here the L3P mutant line that displays phenotypes of disrupted Sonic hedgehog signaling and affects the initiation of cilia formation. A point mutation was mapped in the L3P line to the gene Rsg1, which encodes a GTPase-like protein. The mutation lies within the GTP-binding pocket and disrupts the highly conserved G1 domain. The mutant protein and other centrosomal and IFT proteins still localize appropriately to the basal body of cilia, suggesting that RSG1 GTPase activity is not required for basal body maturation but is needed for a downstream step in axonemal elongation.
纤毛在调节胚胎发育所需的信号通路中发挥着关键作用，包括神经管的正常形成，神经管是大脑和脊髓的前体。正向遗传学筛选被用来产生显示神经管缺陷（NTD）和次级表型的小鼠品系，这些表型可用于探究功能。我们在这里描述 L3P 突变体线，该线显示出 Sonic hedgehog 信号中断的表型，并影响纤毛形成的起始。L3P 线中的点突变被映射到基因 Rsg1，该基因编码一种 GTPase 样蛋白。该突变位于 GTP 结合口袋内，并破坏了高度保守的 G1 结构域。突变蛋白和其他中心体和 IFT 蛋白仍然适当地定位于纤毛的基底体，这表明 RSG1 GTPase 活性对于基底体成熟不是必需的，但对于轴突延伸的下游步骤是必需的。
