Dejima Katsufumi, Kang Sukryool, Mitani Shohei, Cosman Pamela C, Chisholm Andrew D
Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Department of Physiology, Tokyo Women's Medical University, School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA 92037-0407, USA.
Development. 2014 Nov;141(22):4354-65. doi: 10.1242/dev.113266. Epub 2014 Oct 24.
Wnt signals orient mitotic spindles in development, but it remains unclear how Wnt signaling is spatially controlled to achieve precise spindle orientation. Here, we show that C. elegans syndecan (SDN-1) is required for precise orientation of a mitotic spindle in response to a Wnt cue. We find that SDN-1 is the predominant heparan sulfate (HS) proteoglycan in the early C. elegans embryo, and that loss of HS biosynthesis or of the SDN-1 core protein results in misorientation of the spindle of the ABar blastomere. The ABar and EMS spindles both reorient in response to Wnt signals, but only ABar spindle reorientation is dependent on a new cell contact and on HS and SDN-1. SDN-1 transiently accumulates on the ABar surface as it contacts C, and is required for local concentration of Dishevelled (MIG-5) in the ABar cortex adjacent to C. These findings establish a new role for syndecan in Wnt-dependent spindle orientation.
Wnt信号在发育过程中使有丝分裂纺锤体定向，但Wnt信号如何在空间上受到控制以实现精确的纺锤体定向仍不清楚。在此，我们表明秀丽隐杆线虫的syndecan（SDN-1）是响应Wnt信号使有丝分裂纺锤体精确定向所必需的。我们发现SDN-1是秀丽隐杆线虫早期胚胎中主要的硫酸乙酰肝素（HS）蛋白聚糖，并且HS生物合成或SDN-1核心蛋白的缺失会导致ABar卵裂球纺锤体定向错误。ABar和EMS纺锤体都会响应Wnt信号重新定向，但只有ABar纺锤体的重新定向依赖于新的细胞接触以及HS和SDN-1。当ABar与C接触时，SDN-1会短暂地积聚在ABar表面，并且是Dishevelled（MIG-5）在与C相邻的ABar皮层中局部富集所必需的。这些发现确立了syndecan在Wnt依赖的纺锤体定向中的新作用。
