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Lack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors

Author

Listed:
  • Devid Damiani

    (Developmental Neurobiology Unit, Université catholique de Louvain, Institute of Neuroscience
    Developmental Neurobiology Unit, WELBIO, Institute of Neuroscience)

  • André M. Goffinet

    (Developmental Neurobiology Unit, Université catholique de Louvain, Institute of Neuroscience
    Developmental Neurobiology Unit, WELBIO, Institute of Neuroscience)

  • Arthur Alberts

    (Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute)

  • Fadel Tissir

    (Developmental Neurobiology Unit, Université catholique de Louvain, Institute of Neuroscience)

Abstract

The diaphanous homologue Diaph3 (aka mDia2) is a major regulator of actin cytoskeleton. Loss of Diaph3 has been constantly associated with cytokinesis failure ascribed to impaired accumulation of actin in the cleavage furrow. Here we report that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation of the Diaph3 gene causes a massive loss of cortical progenitor cells, with subsequent depletion of intermediate progenitors and neurons, and results in microcephaly. In embryonic brain extracts, Diaph3 co-immunoprecipitates with BubR1, a key regulator of the spindle assembly checkpoint (SAC). Diaph3-deficient cortical progenitors have decreased levels of BubR1 and fail to properly activate the SAC. Hence, they bypass mitotic arrest and embark on anaphase in spite of incorrect chromosome segregation, generating aneuploidy. Our data identify Diaph3 as a major guard of cortical progenitors, unravel novel functions of Diaphanous formins and add insights into the pathobiology of microcephaly.

Suggested Citation

  • Devid Damiani & André M. Goffinet & Arthur Alberts & Fadel Tissir, 2016. "Lack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13509
    DOI: 10.1038/ncomms13509
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