In collaboration with the Leslie-Clarkson lab, we also identified P-cadherin variants in patients with cleft lip, suggesting that it may be a meaningful in vivo contributor to this common condition, either alone, or together with variants in other adherence junction genes.

We think the reason for this elevated demand for cell adhesion strength is to transduce and withstand high actomyosin tensile forces driving lip fusion.

While epithelial disruption of E-cadherin alone does not result in a cleft, combined reduction of both E-cad and P-cadherin, does, indicating that there is a threshold requirement for cadherin-mediated cell adhesion in this process.

She found that RhoA and Kaiso binding domains are totally dispensable for the in vivo function of p120-catenin, but that its cadherin-binding ability is crucial, supporting the importance of cell adhesion in this process.

We also examined the role of Ctnnd1/p120-catenin, variants in which are amongst the most common in humans with cleft lip. Through gene editing, Camilla made a series of mouse mutants to define the in-vivo molecular functions of p120-catenin.

Both pharmacologically and through mouse genetics, we showed that actomyosin contractility in the epithelium is crucial for this tissue fusion process, and that its disruption results in a cleft-lip phenotype.

Camilla developed a new live imaging system to directly visualize cellular dynamics underlying upper lip fusion in the mouse embryo, which revealed highly dynamic localized enrichment of F-actin at the fusion site.

This is awesome! Looking forward to reading it.

We’re so lucky you will join us Semil! Can’t wait!