The Planar Cell Polarity (PCP) signaling system is an evolutionarily conserved genetic module that controls polarized cell behavior in animals and is broadly essential for vertebrate development. Among the many behaviors controlled by PCP signaling is the oriented beating of motile cilia, which is central to generating the fluid flow tht is crucial for homeostasis and function in many organ systems, including the airway. Despite the fact that mutation of PCP genes in humans is associated with diverse structural birth defects, studies of PCP protein dynamics have been largely limited to Drosophila, which unlike mammals is highly amenable to live imaging. The immediate goal of this proposal is to develop and exploit novel tools for exploring the dynamics of PCP proteins via live imaging in a vertebrate ciliated epithelium. Understanding the mechanisms of PCP function is an important challenge in developmental biology, and this proposal will generate new, easily adopted tools for the community. Moreover, the proposed experiments will substantially advance our understanding of vertebrate-specific mechanisms of PCP signaling, providing insights into human structural birth defects such as neural tube defects and congenital limb anomalies.
The Planar Cell Polarity (PCP) signaling system is an evolutionarily conserved genetic module that controls polarized cell behavior in animals and is broadly essential for vertebrate development. The mutation of PCP genes in humans is associated with diverse structural birth defects, including neural tube defects and congenital limb anomalies, and new evidence suggests a potential link between PCP proteins and human breast cancer. Results from this proposal should provide new tools for exploring this important signaling mechanism as well as crucial insights into the vertebrate-specific mechanisms of PCP signaling and its related disorders.
| Butler, Mitchell T; Wallingford, John B (2018) Spatial and temporal analysis of PCP protein dynamics during neural tube closure. Elife 7: |
| Butler, Mitchell T; Wallingford, John B (2017) Planar cell polarity in development and disease. Nat Rev Mol Cell Biol 18:375-388 |
| Adler, Paul N; Wallingford, John B (2017) From Planar Cell Polarity to Ciliogenesis and Back: The Curious Tale of the PPE and CPLANE proteins. Trends Cell Biol 27:379-390 |
| Session, Adam M; Uno, Yoshinobu; Kwon, Taejoon et al. (2016) Genome evolution in the allotetraploid frog Xenopus laevis. Nature 538:336-343 |
| Butler, Mitchell T; Wallingford, John B (2015) Control of vertebrate core planar cell polarity protein localization and dynamics by Prickle 2. Development 142:3429-39 |
