Hope College Biology

Epithelial cell signaling and specification during embryonic development in vertebrates (zebrafish) and invertebrates (C. elegans)

We are interested in how cells communicate with each other during embryogenesis to determine cellular identity, timing of cell divisions and spatial relationships that ultimately form different tissues and organs. Specifically, we focus on the influence of cell adhesion dependent signaling mechanisms during embryogenesis, and how cell-cell contacts affect tissue specification. To investigate these phenomena we use two model organisms: the nematode, Caenorhabditis elegans and the zebrafish, Danio rerio.

In C. elegans, we have cloned a non-receptor tyrosine kinase, called FRK-1, and found that it localizes to, and stabilizes, cadherin-mediated adhesion complexes at the plasma membrane. During early embryonic development in C. elegans, the consequences of losing cell-cell contacts, via loss of FRK-1 function, include the loss of cellular differentiation in the skin cells (called the hypodermis) and inhibition of embryonic enclosure. A secondary effect of losing FRK-1 function is that we observe extra cell numbers in multiple tissue types, the specification of which is driven by a signaling mechanism known as the Wnt pathway. We are currently using a genomic knockout of the frk-1 gene to further investigate the molecular mechanism by which FRK-1 functions on a cellular level during development.

Additionally, we are interested in examining the similarities between FRK-1 homologues in vertebrates and invertebrates. FRK-1 belongs to a non-receptor tyrosine kinase family in vertebrates called the Fes/Fps family, and is most closely related to the Fer kinase. This is of particular interest because Fer kinase expression has been found to be altered in a variety of human cancers. To this end, we have identified the Fer/FRK-1 homologue in zebrafish and are currently investigating the expression pattern and requirement for Fer kinase activity during embryonic development.

By investigating the function in Fer/FRK-1 in both model organisms we aim to uncover novel protein interactions that may ultimately lead to advancements in our knowledge of cellular adhesion and signaling mechanisms in both development and cancer.

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