GEMC1 is a critical regulator of multiciliated cell differentiation

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 motil...

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Detalles Bibliográficos
Autores: Terré, Berta, Piergiovanni, Gabriele, Segura Bayona, Sandra, Gil Gómez, Gabriel, Youssef, Sameh A., Stephan-Otto Attolini, Camille, Wilsch‐Bräuninger, Michaela, Jung, Carole, Rojas, Ana M., Marjanović, Marko, Knobel, Philip A., Palenzuela, Lluís, López Rovira, Teresa, Forrow, Stephen, Huttner, Wieland B., Valverde, Miguel Ángel, Bruin, Alain de, Costanzo, Vincenzo, Stracker, Travis H.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/104023
Acceso en línea:https://hdl.handle.net/2445/104023
Access Level:acceso abierto
Palabra clave:Cèl·lules acústiques
Aparell respiratori
Esterilitat
Hair cells
Respiratory organs
Infertility
Descripción
Sumario: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.