Université Côte D'Azur, CNRS, Inserm, iBV, Nice, France.
Biological Research Centre, Hungarian Academy of Sciences, Institute of Genetics, Hungary.
PLoS Genet. 2020 Apr 23;16(4):e1008758. doi: 10.1371/journal.pgen.1008758. eCollection 2020 Apr.
Left-Right (LR) asymmetry is essential for organ positioning, shape and function. Myosin 1D (Myo1D) has emerged as an evolutionary conserved chirality determinant in both Drosophila and vertebrates. However, the molecular interplay between Myo1D and the actin cytoskeleton underlying symmetry breaking remains poorly understood. To address this question, we performed a dual genetic screen to identify new cytoskeletal factors involved in LR asymmetry. We identified the conserved actin nucleator DAAM as an essential factor required for both dextral and sinistral development. In the absence of DAAM, organs lose their LR asymmetry, while its overexpression enhances Myo1D-induced de novo LR asymmetry. These results show that DAAM is a limiting, LR-specific actin nucleator connecting up Myo1D with a dedicated F-actin network important for symmetry breaking.
左右(LR)不对称对于器官定位、形状和功能至关重要。肌球蛋白 1D(Myo1D)已成为果蝇和脊椎动物中进化保守的手性决定因素。然而,Myo1D 与肌动蛋白细胞骨架之间打破对称性的分子相互作用仍知之甚少。为了解决这个问题,我们进行了双重遗传筛选,以确定新的参与 LR 不对称的细胞骨架因子。我们发现保守的肌动蛋白成核因子 DAAM 是左右发育所必需的关键因子。在缺乏 DAAM 的情况下,器官失去 LR 不对称性,而过表达 DAAM 则增强 Myo1D 诱导的从头 LR 不对称性。这些结果表明,DAAM 是一种限制、LR 特异性肌动蛋白成核因子,将 Myo1D 与一个专门的 F-肌动蛋白网络连接起来,该网络对于打破对称性非常重要。