Emma Feist

Cells within a tissue orient themselves along body axes during development. When cells cannot orient properly, this can cause neural tube defects such as incomplete closure, which impacts animal viability. Cell polarity is determined by the asymmetric distribution of polarity proteins, giving cells their orientation. When cells polarize across a planar field, this is called Planar Cell Polarity (PCP). One of the core PCP proteins, Celsr1, creates complexes at cell junctions with the other core PCP proteins. These are Fzd6 and Vangl2. Fzd6 and Vangl2 will localize towards opposite ends of the cell, each within a complex including Celsr1. This system is self-organizing as feedback within the cell promotes the asymmetrical distribution of PCP proteins. The separate complexes interact at the junction allowing for coordination of polarity between neighbors. Celsr1 is also an atypical cadherin, and calcium is required to form a more rigid structure to allow for binding, which is important for the correct polarization of the core PCP proteins.The PCP pathway also directs hair follicle tilt, providing a clear and easy readout to the underlying cell polarity in the epidermis. In the Abyssinian guinea pig, a remarkable phenotype is observed where there are fur whorls across the body. Our lab hypothesized this was due to a mutation impacting the PCP pathway and then mapped this mutation to a candidate variant in Celsr1 (Celsr1Rough).Though we know this mutation introduces an inframe proline, it is still not known how Celsr1Rough causes the phenotype seen in Abyssinian guinea pigs, or the effects on PCP. We are studying this mutation in CD1 murine keratinocytes, testing the effects of varying exposure times to high calcium as well as differing calcium concentrations. For this study we are measuring cell junction formation through the junction size and enrichment of Celsr1 at these junctions.