Snedeker John, Schock Elizabeth N, Struve Jamie N, Chang Ching-Fang, Cionni Megan, Tran Pamela V, Brugmann Samantha A, Stottmann Rolf W
Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
PLoS One. 2017 Mar 14;12(3):e0173258. doi: 10.1371/journal.pone.0173258. eCollection 2017.
Primary cilia are organelles extended from virtually all cells and are required for the proper regulation of a number of canonical developmental pathways. The role in cortical development of proteins important for ciliary form and function is a relatively understudied area. Here we have taken a genetic approach to define the role in forebrain development of three intraflagellar transport proteins known to be important for primary cilia function. We have genetically ablated Kif3a, Ift88, and Ttc21b in a series of specific spatiotemporal domains. The resulting phenotypes allow us to draw several conclusions. First, we conclude that the Ttc21b cortical phenotype is not due to the activity of Ttc21b within the brain itself. Secondly, some of the most striking phenotypes are from ablations in the neural crest cells and the adjacent surface ectoderm indicating that cilia transduce critical tissue-tissue interactions in the developing embryonic head. Finally, we note striking differences in phenotypes from ablations only one embryonic day apart, indicating very discrete spatiotemporal requirements for these three genes in cortical development.
初级纤毛是从几乎所有细胞伸出的细胞器，对于许多经典发育途径的正常调节是必需的。对于纤毛形态和功能重要的蛋白质在皮质发育中的作用是一个相对研究较少的领域。在这里，我们采用了一种遗传学方法来确定三种已知对初级纤毛功能重要的鞭毛内运输蛋白在前脑发育中的作用。我们在一系列特定的时空域中对Kif3a、Ift88和Ttc21b进行了基因敲除。所产生的表型使我们能够得出几个结论。首先，我们得出结论，Ttc21b的皮质表型不是由于Ttc21b在大脑自身内部的活性所致。其次，一些最显著的表型来自神经嵴细胞和相邻表面外胚层的敲除，这表明纤毛在发育中的胚胎头部转导关键的组织-组织相互作用。最后，我们注意到仅相隔一个胚胎日的敲除所产生的表型存在显著差异，这表明这三个基因在皮质发育中具有非常离散的时空需求。
