Session
Session 1
Board Number
24
Determining how a novel mutation in Fzd6 alters Planar Cell Polarity
Planar cell polarity (PCP) refers to the uniform orientation of cell polarity that specifies the orientation of cells in the plane of a tissue. Cell behaviors and cell movements are oriented along a tissue axis during development directing structural formation, body axis elongation, and neural tube closure. When cells are unable to orient along a tissue axis, severe developmental defects occur. The PCP pathway is regulated by an intercellular signaling complex composed of the core set of PCP membrane proteins: Frizzled (Fzd), Vangl, and Celsr. Of the Fzd proteins, Fzd6 and Fzd3 are responsible for controlling PCP signaling and act redundantly in regulating the polarity of skin. Mutations in Fzd6 alone also impact hair follicle orientation. Specifically, the Fzd6 point mutation (S354I) found in rosette mice causes reversed rather than randomized hair follicle orientation that is demonstrated in Fzd6 KO (Knockout) mice. To determine the impact of the point mutation on Fzd6 function, our goal was to quantify and compare PCP defects in rosette against Fzd6 KO backgrounds without any Fzd3 activity. Quantification of PCP defects was done through measuring hair follicle orientation and neural tube closure defects. Our goal was to find markers that allow us to quantify hair follicle phenotypes in Fzd6KO and rst mutants in a Fzd3 null background with a widefield system. P-Cad and Sox-9 imaging show the cleanest signal when compared to E-Cad and Sox-9. In order to analyze neural tube defects, embryos were imaged for different backgrounds. The Fzd6 rst mutation inhibits Fzd6 function during neural tube closure. The phenotype observed is equivalent to the double knockout mutation (Fzd6 KO/KO; Fzd3 KO/KO). We plan to perform additional matings to analyze neural tube closure defects to determine the placement and severity of the defect. Hair follicle orientation of these mice embryos will also be analyzed using high throughput screening on a widefield scope using P-Cad and Sox-9 molecular markers. The phenotypic characteristics of these mice will reveal the role of the rosette point mutation in the PCP pathway