RT Journal Article
SR Electronic
T1 Regulation of Cilia Abundance in Multiciliated Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 478297
DO 10.1101/478297
A1 Rashmi Nanjundappa
A1 Dong Kong
A1 Kyuhwan Shim
A1 Tim Stearns
A1 Steven L. Brody
A1 Jadranka Loncarek
A1 Moe R. Mahjoub
YR 2018
UL http://biorxiv.org/content/early/2018/12/03/478297.abstract
AB Multiciliated cells (MCC) are specialized epithelia that contain hundreds of motile cilia used to propel fluid over the surface of the cell. To template these cilia, each MCC produces hundreds of centrioles by a process termed centriole amplification. Airway progenitor cells initially contain two parental centrioles that nucleate multiple centrioles at once, and structures called deuterosomes that assemble the vast majority of centrioles during amplification. Remarkably, how each cell regulates the precise number of its centrioles and cilia remains unknown. Here, we investigate mechanisms that establish centriole number in MCC using an ex vivo airway culture model. We show that ablation of parental centrioles, via inhibition of Plk4 kinase, does not perturb deuterosome formation and centriole amplification, nor alter the total complement of centrioles per cell. Airway MCC vary in size and surface area, and exhibit a broad range in centriole number. Quantification of centriole abundance in vitro and in vivo identified a direct relationship between cell-surface area and centriole number. By manipulating cell size and shape, we discovered that centriole number scales with increasing surface area. Collectively, our results demonstrate that parental centrioles and Plk4 are dispensable for deuterosome formation, centriole amplification, and establishment of centriole number. Instead, a cell-intrinsic surface area-dependent mechanism controls centriole and cilia abundance in multiciliated cells.