Planar cell polarity signaling in craniofacial development

Abstract

Out of the several signaling pathways controlling craniofacial development, the role of planar cell polarity (PCP) signaling is relatively poorly understood. This pathway, originally identified as a mechanism to maintain cell polarity within the epithelial cells of the Drosophila wing, has been linked to the proper development of a wide variety of tissues in vertebrates and invertebrates. While many of the pathway members are conserved, it appears that some of the members of the pathway act in a tissue-specific manner. Here, we discuss the role of this pathway in vertebrate craniofacial development, highlighting cranial neural crest migration, skull and palate formation and the role of non-traditional modulators of PCP signaling within this developmental process.

Figure 1

The role of PCP signaling in craniofacial development. The core planar cell polarity (PCP) signaling molecules, Frizzled (Fzd), Disheveled (Dsh) and Van Gogh-like 2 (Vangl2), interact with multiple proteins to transmit planar cell polarity information to and from cells. (A) In migrating neural crest cells, Wnt/PCP signaling activates RhoA to inhibit Rac activity in the trailing edge of the cell. Both Syndecan 4 (Sdc4) and protein tyrosine kinase 7 (Ptk7) can interact with Dsh, while Sdc4 can directly inhibit Rac. (B) During craniofacial cartilage formation, core PCP proteins' interaction with Ror2 and proteoglycans, such as Glypican 4 (Gpc4), inhibit Wnt/β-catenin signaling and activate RhoA and Jun signaling. (C) Transport of the proteins involved in PCP processes by a Sec23/24-dependent mechanism or their modification in the Golgi is essential for their function. A clathrin-mediated endocytosis process requiring R-Spondin 3 (Rspo3) and Wnt5a leads to the removal of Sdc4 and Gpc3 from the membrane. Perturbation of any of these processes affect Wnt/PCP signaling and craniofacial development.