GEMC1 is a critical regulator of multiciliated cell differentiation

Publication date

2016-05

Authors

Terré, Berta
Piergiovanni, Gabriele
Segura-Bayona, Sandra
Gil-Gómez, Gabriel
Youssef, Sameh A
Attolini, Camille Stephan-Otto
Wilsch-Bräuninger, Michaela
Jung, Carole
Rojas, Ana M
Marjanović, Marko

Editors

Advisors

Supervisors

Document Type

Article
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License

taverne

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.

Keywords

cilia, ciliopathy, hydrocephaly, infertility, transcription, Taverne

Citation

Terré, B, Piergiovanni, G, Segura-Bayona, S, Gil-Gómez, G, Youssef, S A, Attolini, C S-O, Wilsch-Bräuninger, M, Jung, C, Rojas, A M, Marjanović, M, Knobel, P A, Palenzuela, L, López-Rovira, T, Forrow, S, Huttner, W B, Valverde, M A, de Bruin, A, Costanzo, V & Stracker, T H 2016, 'GEMC1 is a critical regulator of multiciliated cell differentiation', EMBO Journal, vol. 35, no. 9, pp. 942-960. https://doi.org/10.15252/embj.201592821