One master to rule them all

Abstract

Multiciliated cells rely on the same master regulator as dividing cells to amplify the number of centrioles needed to generate the hair-like structures that coat their cell surface.

Keywords: Plk4; cell biology; centriole; cilia; deuterosome; mouse; multiciliated.

Figure 1.. PLK4 is essential for centriole assembly in both cycling cells and differentiating multiciliated cells.

(A) In the first phase of the cell cycle (known as G1), each cell contains two centrioles (grey cylinders): the mother centriole, which is fully mature and contains appendages, and the daughter centriole, which is younger and appendage-free. These centrioles are tethered together and surrounded by an amorphous mass of protein known as the pericentriolar matrix. As cells replicate their DNA (S-phase), each centriole duplicates to form new ‘procentrioles’ via a mechanism regulated by the enzyme PLK4. The procentrioles then elongate into fully formed centrioles. By the G2 phase of the cycle, cells have two pairs of centrioles, which form the mitotic spindle during mitosis (M-phase). The spindle then segregates the centrioles and the cell’s genetic material evenly among the daughter cells. (B) Multiciliated cells (MCCs) arise from progenitor cells that exit their last mitosis with two centrioles, as shown above. During differentiation, these parental centrioles are amplified via two distinct mechanisms: parental centrioles duplicating multiple times to produce new centrioles (top), or centrioles being built from scratch (bottom) using spheroidal, transitory organelles called deuterosomes. Eventually, all the centrioles mature and migrate to the apical surface where they dock to the membrane and form the cell’s cilia. In progenitor cells lacking the enzyme PLK4, neither of these pathways are functional and the cells are unable to differentiate into multiciliated cells.