Curtin John A, Quint Elizabeth, Tsipouri Vicky, Arkell Ruth M, Cattanach Bruce, Copp Andrew J, Henderson Deborah J, Spurr Nigel, Stanier Philip, Fisher Elizabeth M, Nolan Patrick M, Steel Karen P, Brown Steve D M, Gray Ian C, Murdoch Jennifer N
GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, CM19 5AW, United Kingdom.
Curr Biol. 2003 Jul 1;13(13):1129-33. doi: 10.1016/s0960-9822(03)00374-9.
We identified two novel mouse mutants with abnormal head-shaking behavior and neural tube defects during the course of independent ENU mutagenesis experiments. The heterozygous and homozygous mutants exhibit defects in the orientation of sensory hair cells in the organ of Corti, indicating a defect in planar cell polarity. The homozygous mutants exhibit severe neural tube defects as a result of failure to initiate neural tube closure. We show that these mutants, spin cycle and crash, carry independent missense mutations within the coding region of Celsr1, encoding a large protocadherin molecule [1]. Celsr1 is one of three mammalian homologs of Drosophila flamingo/starry night, which is essential for the planar cell polarity pathway in Drosophila together with frizzled, dishevelled, prickle, strabismus/van gogh, and rhoA. The identification of mouse mutants of Celsr1 provides the first evidence for the function of the Celsr family in planar cell polarity in mammals and further supports the involvement of a planar cell polarity pathway in vertebrate neurulation.
在独立的ENU诱变实验过程中，我们鉴定出了两个具有异常摇头行为和神经管缺陷的新型小鼠突变体。杂合和纯合突变体在柯蒂氏器中感觉毛细胞的定向方面存在缺陷，这表明平面细胞极性存在缺陷。由于未能启动神经管闭合，纯合突变体表现出严重的神经管缺陷。我们发现，这些突变体spin cycle和crash在Celsr1的编码区域内携带独立的错义突变，Celsr1编码一种大型原钙黏蛋白分子[1]。Celsr1是果蝇flamingo/starry night的三个哺乳动物同源物之一，它与卷曲蛋白、散乱蛋白、刺状蛋白、斜视蛋白/梵高蛋白和rhoA一起，对果蝇的平面细胞极性途径至关重要。Celsr1小鼠突变体的鉴定为Celsr家族在哺乳动物平面细胞极性中的功能提供了首个证据，并进一步支持了平面细胞极性途径参与脊椎动物神经胚形成的观点。
