LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility

eLife

Hyang Mi Moon¹  Anthony Wynshaw-Boris²  Liqun Luo³  Simon Hippenmeyer³ 

[1] Department of Pediatrics, Institute for Human Genetics, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States;Department of Pediatrics, Institute for Human Genetics, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States;Department of Genetics and Genome Sciences, Case Western Reserve University, School of Medicine, Cleveland, United States;Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, United States;

关键词: LIS1;    mitosis;    cleavage;    neocortex;    neural progenitor;    embryonic fibroblast;    Mouse;   

DOI  :  10.7554/eLife.51512

来源: publisher

【 摘 要 】

Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human- induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here, we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation.

【 授权许可】

CC BY