Planar Cell Polarity Signaling in Collective Cell Movements During Morphogenesis and Disease

Abstract

Collective and directed cell movements are crucial for diverse developmental processes in the animal kingdom, but they are also involved in wound repair and disease. During these processes groups of cells are oriented within the tissue plane, which is referred to as planar cell polarity (PCP). This requires a tight regulation that is in part conducted by the PCP pathway. Although this pathway was initially characterized in flies, subsequent studies in vertebrates revealed a set of conserved core factors but also effector molecules and signal modulators, which build the fundamental PCP machinery. The PCP pathway in Drosophila regulates several developmental processes involving collective cell movements such as border cell migration during oogenesis, ommatidial rotation during eye development, and embryonic dorsal closure. During vertebrate embryogenesis, PCP signaling also controls collective and directed cell movements including convergent extension during gastrulation, neural tube closure, neural crest cell migration, or heart morphogenesis. Similarly, PCP signaling is linked to processes such as wound repair, and cancer invasion and metastasis in adults. As a consequence, disruption of PCP signaling leads to pathological conditions. In this review, we will summarize recent findings about the role of PCP signaling in collective cell movements in flies and vertebrates. In addition, we will focus on how studies in Drosophila have been relevant to our understanding of the PCP molecular machinery and will describe several developmental defects and human disorders in which PCP signaling is compromised. Therefore, new discoveries about the contribution of this pathway to collective cell movements could provide new potential diagnostic and therapeutic targets for these disorders.

Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals

“…Consistent with the effect on directed keratinocyte elongation, JNK and Rock have been described as components of the planar cell polarity (PCP) pathway (Marlow et al, 2002;Munoz-Soriano et al, 2012;Seo et al, 2010). Accordingly, upon treatment of gastrulating embryos, SP600125, Y27632 and Rockout caused convergent extension defects ( Fig.…”

Partial interchangeability of Fz3 and Fz6 in tissue polarity signaling for epithelial orientation and axon growth and guidance

“…These include: (1) hair follicles and their associated structures in the skin; (2) stereociliary bundles on the apical faces of inner ear sensory hair cells; and (3) motile cilia in the trachea and on the walls of the cerebral ventricles that direct the vectorial movement of mucus and cerebrospinal fluid, respectively. Two processes that involve oriented cell movements -neural tube closure in mammals and the related process of convergent extension in amphibia and fish -also require core PCP gene function (Munoz-Soriano et al, 2012;Tada and Heisenberg, 2012).…”

Protein-tyrosine Pseudokinase 7 (PTK7) Directs Cancer Cell Motility and Metastasis

“…Migrating cells need to arrange both leading edge-rear end polarity consisting of cytoskeleton-driven extension and trafficking of necessary membrane extension and adhesion components (1)(2)(3)(4)(5). Widely expressed protein-tyrosine kinase 7 (PTK7) 3 (also known as colon carcinoma kinase-4, CCK-4) is a member of the receptor protein tyrosine kinase family. In this family of kinases, the kinase-like domain lacks at least one of the usually conserved catalytic residues (6 -8).…”