de Campos-Baptista Maria Ines Medeiros, Holtzman Nathalia Glickman, Yelon Deborah, Schier Alexander F
Department of Molecular and Cellular Biology, Center for Brain Science, Broad Institute, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Dev Dyn. 2008 Dec;237(12):3624-33. doi: 10.1002/dvdy.21777.
Members of the Nodal family regulate left-right asymmetry during vertebrate organogenesis, but it is unclear how Nodal signaling controls asymmetric morphogenesis at the cellular level. We used high-resolution time-lapse imaging in zebrafish to compare the movements of cardiomyocytes in the presence or absence of Nodal signaling. Loss of Nodal signaling in late-zygotic mutants for the Nodal co-receptor one-eyed pinhead (LZoep) abolished the leftward movement of cardiomyocytes. Global heart rotation was blocked but cardiomyocyte neighbor relationships were maintained as in wild type. Cardiomyocytes in LZoep mutants moved more slowly and less directionally than their wild-type counterparts. The phenotypes observed in the absence of Nodal signaling strongly resemble abnormalities found in BMP signaling mutants. These results indicate that a Nodal-BMP signaling cascade drives left-right heart morphogenesis by regulating the speed and direction of cardiomyocyte movement.
Nodal家族成员在脊椎动物器官发生过程中调节左右不对称性,但目前尚不清楚Nodal信号传导如何在细胞水平上控制不对称形态发生。我们利用斑马鱼的高分辨率延时成像技术,比较了在有或没有Nodal信号传导情况下心肌细胞的运动。Nodal共受体独眼针头(LZoep)的合子后期突变体中Nodal信号的缺失消除了心肌细胞的向左运动。整体心脏旋转受阻,但心肌细胞的相邻关系与野生型一样得以维持。LZoep突变体中的心肌细胞比野生型对应细胞移动得更慢,方向性也更差。在没有Nodal信号传导时观察到的表型与BMP信号突变体中发现的异常非常相似。这些结果表明,Nodal-BMP信号级联通过调节心肌细胞运动的速度和方向来驱动左右心脏形态发生。