Dutta Sunit, Sriskanda Shahila, Boobalan Elangovan, Alur Ramakrishna P, Elkahloun Abdel, Brooks Brian P
Unit on Pediatric, Developmental & Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Microarray Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Dev Biol. 2015 Oct 15;406(2):203-11. doi: 10.1016/j.ydbio.2015.08.019. Epub 2015 Aug 29.
The formation of cilia is a fundamental developmental process affecting diverse functions such as cellular signaling, tissue morphogenesis and body patterning. However, the mechanisms of ciliogenesis during vertebrate development are not fully understood. In this report we describe a novel role of the Nlz1 protein in ciliogenesis. We demonstrate morpholino-mediated knockdown of nlz1 in zebrafish causes abnormal specification of the cells of Kupffer's vesicle (KV); a severe reduction of the number of cilia in KV, the pronephros, and the neural floorplate; and a spectrum of later phenotypes reminiscent of human ciliopathies. In vitro and in vivo data indicate that Nlz1 acts downstream of Foxj1a and Wnt8a/presumed canonical Wnt signaling. Furthermore, Nlz1 contributes to motile cilia formation by positively regulating Wnt11/presumed non-canonical Wnt signaling. Together, our data suggest a novel role of nlz1 in ciliogenesis and the morphogenesis of multiple tissues.
纤毛的形成是一个影响多种功能的基本发育过程，如细胞信号传导、组织形态发生和身体模式形成。然而，脊椎动物发育过程中纤毛发生的机制尚未完全了解。在本报告中，我们描述了Nlz1蛋白在纤毛发生中的新作用。我们证明，在斑马鱼中，吗啉代介导的nlz1敲低会导致库普弗囊泡（KV）细胞的异常特化；KV、前肾和神经底板中纤毛数量严重减少；以及一系列类似于人类纤毛病的后期表型。体外和体内数据表明，Nlz1在Foxj1a和Wnt8a/假定的经典Wnt信号传导下游起作用。此外，Nlz1通过正向调节Wnt11/假定的非经典Wnt信号传导促进运动性纤毛的形成。总之，我们的数据表明nlz1在纤毛发生和多个组织的形态发生中具有新作用。
