RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells Journal Article


Author(s): Sedzinski, Jakub; Hannezo, Edouard; Tu, Fan; Biro, Maté; Wallingford, John B
Article Title: RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells
Affiliation
Abstract: Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain. Analysis of cell shapes suggests that RhoA alters the balance of forces exerted on the MCC apical surface. Finally, quantitative time-lapse imaging and fluorescence recovery after photobleaching studies argue that RhoA works in concert with Fmn1 to control assembly of the specialized apical actin network in MCCs. These data provide new molecular insights into epithelial apical surface assembly and could also shed light on mechanisms of apical lumen formation.
Keywords: actin; Apical emergence; Arp2/3; Fmn1; Multiciliated cells; RhoA
Journal Title: Journal of Cell Science
Volume: 130
Issue 2
ISSN: 1477-9137
Publisher: Company of Biologists  
Date Published: 2017-01-01
Start Page: 420
End Page: 428
DOI: 10.1242/jcs.194704
Notes: We thank the Wallingford laboratory members for experimental suggestions and critical reading of the manuscript. This work was funded by a European Molecular Biology Organization (EMBO) Long Term Fellowship to J.S.; a Research Fellowship from Trinity College, University of Cambridge a Wellcome Trust fellowship (110326/Z/15/Z) and Fondation Bettencourt Schueller Young Researcher Prize to E.H; a Cancer InstituteNSWEarly Career Researcher fellowship (13/ECF/1-25) and a Cancer Australia and Cure Cancer Australia Foundation project grant (1070498) to M.B.; and grants from the National Heart, Lung, and Blood Institute (HL117164) and National Institute of General Medical Sciences (GM074104) to J.B.W. This work was initiated at the New Quantitative Approaches to Morphogenesis Workshop at University of California, Santa Barbara, which is funded in part by the National Science Foundation (PHY11-25915) and the National Institute of General Medical Sciences (GM067110-05). Deposited in PMC for release after 12 months.
Open access: no