Investigating the cytoplasmic role of E2F4 in multiciliogenesis

The E2F family of transcription factors plays essential transcriptional roles in many cellular processes including proliferation and terminal differentiation. Transgenic mouse models have established that E2F4 is necessary for multiciliogenesis in the airway epithelia. Here we show that E2F4 plays two distinct roles in multiciliogenesis. In early stages, it functions in the nucleus to transcriptionally activate centriole biogenesis genes required for cilia formation. Subsequently, E2F4 locates to the cytoplasm and colocalizes with the early components of deuterosome complexes, which enable the large-scale amplification of basal bodies, from which cilia are assembled. Reconstitution experiments using E2f4-deficient tracheal precursor cells in an in vitro differentiation assay, showed that both nuclear and cytoplasmic forms of E2F4 are essential for multiciliogenesis.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Hazan, Renin.

Advisor dc:contributor.advisor

• Jacqueline A. Lees.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/127133

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/127133