CAM-1

            We initially chose to focus on cam-1 because its mutant phenotypes were both interesting and unusual. Cells that migrated posteriorly during embryogenesis often failed to migrate to their normal positions, whereas cells that migrated anteriorly, including the hermaphrodite-specific neurons (HSNs), often migrated too far (Figure). These data suggested that CAM-1 was involved in specifying the final position of migrating cells, a process about which we knew relatively little. In particular, few proteins involved in specifying cell position have been identified. In our analysis of cam-1 mutants, we also noticed that loss of cam-1 resulted in defects in the orientation of polarity of specific cells, suggesting that CAM-1 might function in specifying cell polarity as well. The finding that CAM-1 is required for multiple processes has provided an initial inroad into studying them at the molecular level.

            To identify the gene that was defective in cam-1 mutants, I cloned the cam-1 gene and showed that it encodes a receptor tyrosine kinase (RTK)-related protein that is the sole C. elegans member of a subfamily of RTKs called the Rors. Protein kinases add phosphate groups to target proteins, thereby modulating their activity. RTKs are a specific class of protein kinases, which act as cell surface receptor proteins that mediate many developmental decisions. Ror genes have been identified in multiple organisms, but little is known about their function. Interestingly, mutation in one of the two human Rors, hRor2, results in either recessive Robinow syndrome or dominant brachydactyly B, which are both bone development disorders. Therefore elucidating the functions of cam-1 and the pathways by which it acts will provide critical information not only about the process of cell migration but also about human disease.