MSc Exit Seminar – Saba Haroon (Tepass lab)

MSc Exit Seminar

Tuesday October 6th, 10:10 am – Ramsay Wright Building, Rm. 432

Saba Haroon (Tepass lab) 

“Examining the Function of β-catenin at Adherens Junctions during Dorsal Closure and the Formation of the Ventral Epidermis in Drosophila“

Abstract

Adherens junctions (AJs) are made of Cadherin-Catenin Complexes (CCCs); each CCC contains DE-cadherin that binds to p120catenin and β-catenin (Armadillo in Drosophila). Monomeric α-Catenin in turn binds to β-catenin linking the CCC to the actin cytoskeleton. One open question concerning the function of β-catenin is whether it functions only to physically link DE-cadherin to α-Catenin. Alternatively, β-catenin could also act as an important regulator of AJ stability during morphogenetic movements. It has been proposed, for example, that phosphorylation of β-catenin regulates the interaction between β-catenin and its binding partners. Here I have addressed the question whether β-catenin acts only as a physical linker or also has important regulatory functions in Drosophila AJs.

Morphogenetic movements give shape to the developing embryo. One of these morphogenetic movements in Drosophila is dorsal closure. Dorsal closure (DC) is a process by which the dorso-lateral epidermis of an embryo converges to conceal a dorsal opening that is covered by the extra-embryonic amnioserosa. The adhesion between amnioserosa and epidermal cells is regulated to withstand forces during DC while amnioserosa cells contract and are internalized. A second process examined is the formation of the ventral epidermis that undergoes several dynamic movements including cell ingression, cell division, and convergence-extension. DC fails and the ventral epidermis loses integrity when AJs are compromised.

I found that DC defects in embryos lacking DE-cadherin can be partially rescued by fusion proteins that directly link DE-cadherin to α-Catenin without recruiting Armadillo/β-catenin to AJs. This suggests that Armadillo has an important function at AJs for normal DC apart from its role as a linker between DE-cadherin and α-Catenin. In contrast, ventral defects can be completely rescued by a fusion protein of DE-cadherin and α-Catenin that fails to recruit Armadillo, indicating that Armadillo has no essential regulatory function at AJs in this tissue. In addition, in embryos lacking Armadillo, I found that DC defects can be partially rescued by the expression of DE-cadherin α-Catenin fusion proteins. I speculate that the lack of a complete rescue is due to compromised Wnt signalling pathway of which Armadillo is a core component and which has previously been implicated in DC. Together, my results are consistent with the view that Armadillo/β-catenin has a general essential function in linking DE-cadherin to α-Catenin but a tissue-specific regulatory role in controlling AJ dynamics required for morphogenesis.

Ramsay Wright is a wheelchair accessible building.