Date of Award

1-1-2018

Document Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

First Advisor

Scott A. Nichols

Keywords

Adherens junctions, Cell adhesion, Evo-devo, Focal adhesions, Multicellularity, Porifera

Abstract

A fundamental requirement for multicellularity is cell adhesion. This includes mechanisms by which cells adhere to each other and to their secreted extracellular matrix (ECM). Two well characterized adhesion complexes in animals include: 1) adherens junctions (AJs), which are involved in cell-cell adhesion and composed of cadherin receptors, p120-, α- and β-catenin, and 2) focal adhesions (FAs), which are involved in cell-ECM adhesion and include proteins such as integrins, vinculin, paxillin, talin and focal adhesion kinase (FAK). The molecular components of AJs are widely conserved in animals, and largely absent in non-animals. In contrast, the molecular components of FAs have more ancient origins and can be traced to the last common ancestor of Holozoa. The wide distribution of these structures in animals suggests that they evolved early, possibly coincident with multicellularity. However, a challenge to this perspective is that previous studies of sponges - a divergent animal lineage - indicated that their tissues are organized primarily by an alternative, sponge-specific cell adhesion complex called the 'aggregation factor'. But, a recent study in Ephydatia muelleri places the AJ protein β-catenin at AJ-like structures in cell-cell contacts, and at FA-like structures in the cell-ECM interface. This led us to further examine the focal adhesion proteins vinculin, focal adhesion kinase and integrin in sponges. Our data show that vinculin localizes to both cell-cell and cell-ECM contacts has biochemical and structural properties similar to vertebrate vinculin. These data provide compelling evidence that sponge tissues are indeed organized like epithelia in other animals and support that AJ- and FA-like structures extend to the earliest periods of animal evolution. However, the colocalization of FA-proteins with β-catenin at these structures indicates a fundamental difference between the organization and molecular composition of cell junctions in sponge tissues compared to bilaterian epithelia. This interpretation was functionally examined through pharmacological perturbation of FAK to test for cell-adhesion and cell-migration phenotypes.

Provenance

Recieved from ProQuest

Rights holder

Jennyfer Mora Mitchell

File size

143 p.

File format

application/pdf

Language

en

Discipline

Cellular biology, Evolution & development, Zoology

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