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This week we profile a recent publication in Cell Reports from Amanda Haage
(fourth from left) and the laboratory of Dr. Guy Tanentzapf (centre) at UBC.

Can you provide a brief overview of your lab’s current research focus?

Our lab uses cutting edge genetics, imaging, molecular and quantitative approaches to understand how cell junctions contribute to the development and maintenance of tissues.

What is the significance of the findings in this publication?

Here we described a new transgenic mouse model to investigate how cell to extracellular matrix (ECM) adhesions are regulated in the context of a whole organism. The mutation we introduced prevents an important regulatory function of Talin-1, called autoinhibition. Though mice lacking Talin-1 autoinhibition are viable and fertile, they heal slower when challenged with a wounding model in the skin.

We show, using quantitative image analysis, that this is due to changes at the cellular level. Fibroblasts derived from these mice, which lack talin autoinhibition, increase both the strength and stability of their cell-ECM adhesions. This leads to these cells being less dynamic, including moving slower both in vitro and in vivo. Overall, we find that a significant wholesale increase in cell-ECM adhesion prevents the dynamic processes necessary to maintain whole animal homeostasis.

What are the next steps for this research?

This was our first step into transgenic mouse models, building on the work we’ve done in this field previously in drosophila. We’re looking forward to drawing more parallels on how cell-ECM adhesions are regulated between flies and mice with a variety of new transgenic models in both systems. Specifically for talin autoinhibition, we have identified several other phenotypes presented by these mice. We are currently characterizing a delayed migration of melanoblasts, which are important for   development, as well as a blood clotting defect that models human clotting disorders.

This work was funded by:

This study was supported by CIHR Operating Grants to G.T. (MOP-285391) and L.L. (MOP-119357), a CIHR grant-in-aid to D.J.G., a CIHR post-doctoral fellowship to C.T.T., a Canada Foundation for Innovation Grant to S.P. (#34473), and NSERC Discovery Grants to L.L. (386979-12) and S.P (RGPIN-2015-05114). In addition, B.T.G is funded by Biotechnology and Biological Sciences Research Council grant (BB/N007336/1) and B.T.G and A.W are funded by a Human Frontier Science Program grant (RGP00001/2016).

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