Regulation of Stem Cell-like Behavior by the Non-Receptor Tyrosine Kinase, FRK-1, during Post-embryonic Development in the Nematode, Caenorhabditis elegans.
Dr. Aaron Putzke, Hope College
FRK-1, a homologue of the mammalian Fer kinase, is a non-receptor tyrosine kinase which we have found to be required for differentiation and maintenance of epithelial cell types during morphogenesis in the nematode, Caenorhabditis elegans. Expression analysis shows that FRK-1 is expressed primarily in epithelial cells, where it is highly localized to the cell-cell contacts, to stabilize adhesion complexes, until mitosis when it appears strongly nuclear localized. In the absence of maternal FRK-1, an epithelial subset of cell known as the hypodermal cells (skin) are specified but not fully differentiated indicating that FRK-1 is required for maintaining hypodermal differentiation in developing embryos. Furthermore, we have demonstrated a requirement for FRK-1 during embryonic endoderm (gut) proliferation, where in the absence of FRK-1, gut cells hyperproliferate via the non-canonical Wnt signaling mechanism. Additionally, we have characterized a genomic knockout of frk-1 which eliminates only zygotic FRK-1 expression and results in early larval lethality. In mutants homozygous for the frk-1 deletion we have observed an excess number of lateral hypodermal cells, known as seam cells, and loss of asymmetry in the stem cell-like divisions within the seam cell linage. More specifically, our data shows a loss of seam cell fate within the V1-V6 seam cells, resulting in smaller cells that appear to have differentiated as non-seam, hypodermal cells. We are investigating the mechanism by which the loss of FRK-1 causes this cell fate switch and whether FRK-1 translocation to the nucleus during mitosis is required for the stem cell-like self-renewal exhibited by seam cells during post-embryonic development in C. elegans.
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