Regulation of Seam Cell Function by the Non-Receptor Tyrosine Kinase, FRK-1, in C. Elegans

We are characterizing the role of a non-receptor tyrosine kinase, FRK-1, during post-embryonic development using the nematode, Caenorhabditis elegans. To determine the role of FRK-1 in development, the effects of the absence of frk-1 were analyzed in stem cell-like seam cells. In the absence of FRK-1 function we have observed the loss of asymmetric division in the seam cells and subsequent loss of progression to adulthood. We have begun to analyze how FRK-1 depleted larval seam cells behave compared to differentiated adult seam cells, thereby preventing further development. Using the frk-1 knockout (ok760) VC558 line of C. elegans, the identity of seam cells and the signaling involved can be further studied with the use of an optimized antibody staining protocol to assess the identity of the mutant seam cells and hypodermal cells present and through crosses with worm lines that contain florescent protein promoters. Establishing the function of FRK-1 in C. elegans would allow for not only a better understanding of development, but could help assess the role of Fer in humans. Fer has previously been shown to be over expressed in prostate cancer and deleted in acute myeloid leukemia (Rubinfeld et al., 1997; Munemitsu et al., 1995), so the determination of the function of FRK-1 could thereby potentially provide insight into more fully understanding and preventing cancer. Thus, having a more complete awareness of how cells adhere and signal to one another and respond to their environment will not only allow the intricacies involved in development to be further comprehended, but could ultimately have greater implications to stem cells and cancer (Reya et al. 2001)