原本精确对称的胚胎如何决定左右?一直是发育生物学的未解之谜。
纤毛(cilia)是大多数细胞上都具有的毛发样结构,研究人员实验发现:胚胎中出现纤毛是胚胎左右成型的转折点。这些简单的纤毛结构不仅与发育过程中,左右模式的形成有关,也可以帮助脑、肺、眼和肾中的体液流动,帮助嗅觉、视觉和生殖系统发育。已知糖尿病和肥胖症等疾病都与纤毛缺陷有关。破坏纤毛的功能或者改变纤毛的活动性,会导致全身性疾病。另外最近有证据显示,纤毛在骨骼发育和大脑活动中也扮演重要的角色。
最近,Salk 生物学研究所Juan Carlos Izpisúa Belmonte博士率领的研究小组,在斑马鱼胚胎中鉴别出一种因子Duboraya,而解释了发育早期阶段鱼胚胎中,控制纤毛形成的分子过程,研究人员改变duboraya基因的功能后发现,纤毛的形成发生问题。
纤毛位于胚胎腹侧表面,可向左侧传递化学信号,形成的化学浓度梯度能够告诉干细胞怎样发育、向哪里发育。当纤毛功能减弱,心脏、肺和肾等器官最终可能会移向错误的发育地点。
研究结果将早期发育信号与纤毛形成以及纤毛,与控制斑马鱼胚胎左右模式中的功能联接起来。这项研究结果将发表于Nature Genetics中。
英文原文:
Regulation of primary cilia formation and left-right patterning in zebrafish by a noncanonical Wnt signaling mediator, duboraya
dubWntPrimary cilia are microtubule-based organelles that project from the surface of nearly every animal cell1. Although important functions of primary cilia in morphogenesis and tissue homeostasis have been identified, the mechanisms that control the formation of primary cilia are not understood. Here we characterize a zebrafish gene, termed duboraya (dub), that is essential for ciliogenesis. Knockdown of dub in zebrafish embryos results in both defects in primary cilia formation in Kupffer's vesicle and randomization of left-right organ asymmetries. We show that, at the molecular level, the function of dub in ciliogenesis is regulated by phosphorylation, which in turn depends on Frizzled-2–mediated noncanonical Wnt signaling. We also provide evidence that, at the cellular level, dub function is essential for actin organization in the cells lining Kupffer's vesicle. Taken together, our findings identify a molecular factor that links noncanonical Wnt signaling with the control of left-right axis specification, and provide an entry point for analyzing the mechanisms that regulate primary cilia formation.