Mitotic Internalization of Planar Cell Polarity Proteins Preserves Tissue Polarity

Planar cell polarity (PCP) is the collective polarization of cells along the epithelial plane, a process best understood in the terminally differentiated Drosophila wing. Proliferative tissues such as mammalian skin also display PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically-distributed PCP components risk mislocalisation or unequal inheritance, which could have profound consequences on the long-range propagation of polarity. Here, we show that when mouse epidermal basal progenitors divide, PCP components are selectively internalized into endosomes, which are inherited equally by daughter cells. Following mitosis, PCP proteins are recycled to the cell surface where asymmetry is re-established by a process reliant upon neighbouring PCP. A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot mitotically internalize, exhibit perturbed hair follicle angling, a hallmark of defective PCP. This underscores the physiological relevance and importance of this novel mechanism for regulating polarity during cell division.