Polarity and Morphogenesis‐‐‐ the Planar Cell Polarity Pathway in Mammalian Embryogenesis

Abstract

Originally identified in flies, the planar cell polarity (PCP) pathway is crucial in establishing the cellular polarity in the plane of the epithelium, perpendicular to the apical‐basal axis of the cell. In frogs and zebrafish, homologous PCP genes regulate directional cell behavior to mediate polarized tissue morphogenesis. In the mouse, we and others have found that a highly conserved mammalian PCP pathway regulates both cell polarity and morphogenetic movement to assemble cells into tissues and organs with distinct anatomical forms and structures. For example, auditory sensory hair cells develop uniformly oriented stereocilia on the apical surface and PCP proteins localize asymmetrically on the apical membrane during this process. Mutations in PCP genes disrupt polarized membrane distribution of other PCP proteins and cause randomized orientation of stereocilia. We have also found that the PCP pathway is essential for coordinated lengthening and narrowing of the neural plate during neural tube closure. The PCP pathway is also required for outflow tract formation in the heart and our genetic studies pinpointed a specific role of this pathway in cardiomyocytes derived from the secondary heart field. While the detailed cellular mechanisms are yet to be defined, the mammalian PCP pathway is undoubtedly a critical force in shaping various tissues and organs and may underlie a number of birth defects in humans.