4.6 Review

Transcriptional regulation of multiciliated cell differentiation

Journal

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 110, Issue -, Pages 51-60

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2020.04.007

Keywords

Multiciliated cells; E2F4; E2F5; GEMC1; MCIDAS; FOXJ1; MYB; p73; NOTCH; AHR; TRRAP; CCNO; CDC20B; Centriole; Basal body; Airway; Ependyma; Germline; Ciliopathy; Infertility; Hydrocephalus

Funding

  1. Spanish Ministry of Science, Innovation and Universities [MCIU: PGC2018-095616-B-I00/GINDATA]
  2. Spanish Ministry of Science, Innovation and Universities (FEDER)
  3. Centres of Excellence Severo Ochoa award
  4. CERCA Programme
  5. Severo Ochoa FPI fellowship (MCIU/Fondo Social Europeo) [BES-2017-081695]

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The differentiation program of multiciliated cells is initiated by GEMC1 and MCIDAS, which activate key transcription factors to control the generation of multiple motile cilia. To support this, massive centriole amplification is required, along with the generation of unique deuterosomes and extensive remodeling of the cytoskeleton.
Multiciliated cells (MCC) project dozens to hundreds of motile cilia from the cell surface to generate fluid flow across epithelial surfaces or turbulence to promote the transport of gametes. The MCC differentiation program is initiated by GEMC1 and MCIDAS, members of the geminin family, that activate key transcription factors, including p73 and FOXJ1, to control the multiciliogenesis program. To support the generation of multiple motile cilia, MCCs must undergo massive centriole amplification to generate a sufficient number of basal bodies (modified centrioles). This transcriptional program involves the generation of deuterosomes, unique structures that act as platforms to regulate centriole amplification, the reactivation of cell cycle programs to control centriole amplification and release, and extensive remodeling of the cytoskeleton. This review will focus on providing an overview of the transcriptional regulation of MCCs and its connection to key processes, in addition to highlighting exciting recent developments and open questions in the field.

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