1. Developmental Biology
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LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility

  1. Hyang Mi Moon  Is a corresponding author
  2. Simon Hippenmeyer
  3. Liqun Luo
  4. Anthony Wynshaw-Boris  Is a corresponding author
  1. Stanford University, United States
  2. Institute of Science and Technology Austria, Austria
  3. Howard Hughes Medical Institute, Stanford University, United States
  4. Case Western Reserve University, University Hospitals Cleveland Medical Center, United States
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Cite this article as: eLife 2020;9:e51512 doi: 10.7554/eLife.51512

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

Author details

  1. Hyang Mi Moon

    Neurosurgery, Stanford University, Stanford, United States
    For correspondence
    chorong@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2755-3767
  2. Simon Hippenmeyer

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2279-1061
  3. Liqun Luo

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5467-9264
  4. 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.
    ORCID icon "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

Reviewing Editor

  1. Mohan K Balasubramanian, University of Warwick, United Kingdom

Publication history

  1. Received: September 2, 2019
  2. Accepted: March 10, 2020
  3. Accepted Manuscript published: March 11, 2020 (version 1)
  4. Version of Record published: April 1, 2020 (version 2)

Copyright

© 2020, Moon et al.

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.

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