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

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Abstract

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.

Data availability

All data analyzed during this study and its analysis has been described in the manuscript.

Article and author information

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Hyang Mi Moon

Neurosurgery, Stanford University, Stanford, United States

For correspondence
chorong@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2755-3767
Simon Hippenmeyer

Institute of Science and Technology Austria, Klosterneuburg, Austria

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2279-1061
Liqun Luo

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5467-9264
Anthony Wynshaw-Boris

Department of Genetics and Genome Sciences, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, United States

For correspondence
ajw168@case.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2780-1540

Funding

National Institute of Neurological Disorders and Stroke (NIH-R01-NS041030)

Anthony Wynshaw-Boris

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH-R01-HD047380)

Anthony Wynshaw-Boris

University of California, San Francisco (Graduate Student Research Award)

Hyang Mi Moon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal care and experimental procedures were approved by the University of California, San Francisco Institutional Animal Care and Use Committee (IACUC) in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Protocol ID: 13446

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.