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Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis
Munemasa Mori1, Renin Hazan2, Paul S Danielian2
1Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care, Columbia University Medical Center, New York City, New York 10032, USA.
Nature Communications
|July 5, 2017
Summary
The transcription factor E2f4 initiates multiciliogenesis by translocating to the cytoplasm to form organizing centers. This process is crucial for centriole amplification and normal ciliogenesis, offering insights into related diseases.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Abnormal multiciliated cell development is linked to chronic airway diseases, hydrocephalus, and infertility.
- Multiciliogenesis involves transcriptional programs and cytoplasmic structures for centriole amplification and basal body generation.
Purpose of the Study:
- To elucidate the mechanism initiating multiprotein complex formation for centriole amplification in epithelial progenitors.
- To identify the role of transcription factor E2f4 in multiciliogenesis.
Main Methods:
- Utilized genetically altered mice with E2F4 mutations.
- Investigated nucleocytoplasmic translocation of E2f4.
- Analyzed the formation of cytoplasmic organizing centers and deuterosomes.
Main Results:
- E2f4's nucleocytoplasmic translocation triggers multiciliogenesis.
- E2f4 forms apical cytoplasmic organizing centers for deuterosome assembly.
- Centriole amplification is dependent on these E2f4-mediated cytoplasmic structures; absence of cytoplasmic E2f4 halts multiciliogenesis.
Conclusions:
- E2f4 integrates nuclear and cytoplasmic events essential for centriole amplification.
- This finding provides new perspectives on ciliogenesis, ciliopathies, and cancer.
- E2f4 is a key regulator initiating the formation of essential structures for multiciliogenesis.
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