Zhang Pei, Chen Jiwei, Wang Xiangchuan, Geng Yingchao, Sun Liangyu, Zhang Hongjie
Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China.
Biological Imaging and Stem Cell Core, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China.
Development. 2023 Jan 15;150(2). doi: 10.1242/dev.200840. Epub 2023 Jan 20.
Organ morphogenesis needs orchestration of a series of cellular events, including cell division, cell shape change, cell rearrangement and cell death. Cytokinesis, the final step of cell division, is involved in the control of organ size, shape and function. Mechanistically, it is unclear how the molecules involved in cytokinesis regulate organ size and shape. Here, we demonstrate that the centralspindlin complex coordinates cell division and epithelial morphogenesis by regulating cytokinesis. Loss of the centralspindlin components CYK-4 and ZEN-4 disrupts cell division, resulting in altered cell arrangement and malformation of the Caenorhabditis elegans spermatheca. Further investigation revealed that most spermathecal cells undergo nuclear division without completion of cytokinesis. Germline mutant-based analyses suggest that CYK-4 regulates cytokinesis of spermathecal cells in a GTPase activator activity-independent manner. Spermathecal morphology defects can be enhanced by double knockdown of rho-1 and cyk-4, and partially suppressed by double knockdown of cdc-42 and cyk-4. Thus, the centralspindlin components CYK-4 and ZEN-4, together with RHO-1 and CDC-42, are central players of a signaling network that guides spermathecal morphogenesis by enabling completion of cytokinesis.
器官形态发生需要一系列细胞事件的协调,包括细胞分裂、细胞形状改变、细胞重排和细胞死亡。胞质分裂是细胞分裂的最后一步,参与器官大小、形状和功能的控制。从机制上讲,尚不清楚参与胞质分裂的分子如何调节器官大小和形状。在这里,我们证明中央纺锤体复合物通过调节胞质分裂来协调细胞分裂和上皮形态发生。中央纺锤体成分CYK-4和ZEN-4的缺失会破坏细胞分裂,导致秀丽隐杆线虫受精囊的细胞排列改变和畸形。进一步研究发现,大多数受精囊细胞经历核分裂但未完成胞质分裂。基于种系突变体的分析表明,CYK-4以不依赖GTPase激活剂活性的方式调节受精囊细胞的胞质分裂。rho-1和cyk-4的双敲低可增强受精囊形态缺陷,而cdc-42和cyk-4的双敲低可部分抑制该缺陷。因此,中央纺锤体成分CYK-4和ZEN-4,以及RHO-1和CDC-42,是一个信号网络的核心参与者,该网络通过使胞质分裂完成来引导受精囊形态发生。