Shah Pavak K, Tanner Matthew R, Kovacevic Ismar, Rankin Aysha, Marshall Teagan E, Noblett Nathaniel, Tran Nhan Nguyen, Roenspies Tony, Hung Jeffrey, Chen Zheqian, Slatculescu Cristina, Perkins Theodore J, Bao Zhirong, Colavita Antonio
Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Dev Cell. 2017 Apr 24;41(2):195-203.e3. doi: 10.1016/j.devcel.2017.03.024.
Formation and resolution of multicellular rosettes can drive convergent extension (CE) type cell rearrangements during tissue morphogenesis. Rosette dynamics are regulated by both planar cell polarity (PCP)-dependent and -independent pathways. Here we show that CE is involved in ventral nerve cord (VNC) assembly in Caenorhabditis elegans. We show that a VANG-1/Van Gogh and PRKL-1/Prickle containing PCP pathway and a Slit-independent SAX-3/Robo pathway cooperate to regulate, via rosette intermediaries, the intercalation of post-mitotic neuronal cell bodies during VNC formation. We show that VANG-1 and SAX-3 are localized to contracting edges and rosette foci and act to specify edge contraction during rosette formation and to mediate timely rosette resolution. Simultaneous loss of both pathways severely curtails CE resulting in a shortened, anteriorly displaced distribution of VNC neurons at hatching. Our results establish rosette-based CE as an evolutionarily conserved mechanism of nerve cord morphogenesis and reveal a role for SAX-3/Robo in this process.
多细胞玫瑰花结的形成与解体可在组织形态发生过程中驱动汇聚延伸（CE）型细胞重排。玫瑰花结动力学受平面细胞极性（PCP）依赖性和非依赖性途径的调控。在此，我们表明CE参与了秀丽隐杆线虫腹侧神经索（VNC）的组装。我们发现，一条包含VANG-1/凡·高和PRKL-1/棘蛋白的PCP途径以及一条不依赖Slit的SAX-3/轮状蛋白途径，通过玫瑰花结中间体协作，在VNC形成过程中调节有丝分裂后神经元细胞体的插入。我们发现VANG-1和SAX-3定位于收缩边缘和玫瑰花结焦点，并在玫瑰花结形成过程中确定边缘收缩，以及介导玫瑰花结的适时解体。两条途径同时缺失会严重削弱CE，导致孵化时VNC神经元分布缩短且向前移位。我们的结果确立了基于玫瑰花结的CE作为神经索形态发生的一种进化保守机制，并揭示了SAX-3/轮状蛋白在此过程中的作用。
