GEMC1 is a critical regulator of multiciliated cell differentiation

Berta Terre, Gabriele Piergiovanni, Sandra Segura-Bayona, Gabriel Gil-Gomez, Sameh A. Youssef, Camille Stephan-Otto Attolini, Michaela Wilsch-Braeuninger, Carole Jung, Ana M. Rojas, Marko Marjanovic, Philip A. Knobel, Lluis Palenzuela, Teresa Lopez-Rovira, Stephen Forrow, Wieland B. Huttner, Miguel A. Valverde, Alain de Bruin, Vincenzo Costanzo, Travis H. Stracker*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    43 Citations (Scopus)

    Abstract

    The generation of multiciliated cells (MCCs) is required for the proper function of many tissues, including the respiratory tract, brain, and germline. Defects in MCC development have been demonstrated to cause a subclass of mucociliary clearance disorders termed reduced generation of multiple motile cilia (RGMC). To date, only two genes, Multicilin (MCIDAS) and cyclin O (CCNO) have been identified in this disorder in humans. Here, we describe mice lacking GEMC1 (GMNC), a protein with a similar domain organization as Multicilin that has been implicated in DNA replication control. We have found that GEMC1-deficient mice are growth impaired, develop hydrocephaly with a high penetrance, and are infertile, due to defects in the formation of MCCs in the brain, respiratory tract, and germline. Our data demonstrate that GEMC1 is a critical regulator of MCC differentiation and a candidate gene for human RGMC or related disorders.

    Original languageEnglish
    Pages (from-to)942-960
    Number of pages19
    JournalThe EMBO Journal
    Volume35
    Issue number9
    DOIs
    Publication statusPublished - 2-May-2016

    Keywords

    • cilia
    • ciliopathy
    • hydrocephaly
    • infertility
    • transcription
    • MUCOCILIARY CLEARANCE DISORDER
    • NOTCH SIGNALING CONTROLS
    • MULTIPLE MOTILE CILIA
    • CENTRIOLE BIOGENESIS
    • FUNCTIONAL GENOMICS
    • ALZHEIMERS-DISEASE
    • TRANSCRIPTION FACTORS
    • REDUCED GENERATION
    • DNA-REPLICATION
    • EPENDYMAL CELLS

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