An important question in developmental genetics is how distinct cell types migrate, change shape and interact in a coordinated manner to form an organ. Caenorhabditis elegans, with its powerful genetics, invariant cell lineage and optical transparency that allows for live-imaging microscopy during embryo development, is an excellent tool to study cellular migration and coordination of morphogenesis during organ development. The C. elegans pharynx is a muscular feeding organ of the upper digestive tract. The pharynx is relatively simple organ, it consists of about 95 cells, but contains diverse cell types including muscle, neuronal, structural, epithelial, and secretory gland cells. During pharynx morphogenesis, these diverse cell types coordinate their movements to rearrange themselves from a “ball of cells” into an extended tubular structure. In my lab, we have focused our studies on the development of the pharyngeal gland cells. Live imaging studies have been used to determine that these cells, in particular the dorsal gland cell, create a unicellular extension through a process called retrograde extension. During this morphogenic process, the cell is born in the anterior aspect of the pharyngeal primordium and migrates to the posterior pharynx leaving a unicellular projection in its migratory wake.
Progress in understanding the molecular underpinnings to retrograde extension will be discussed. A forward genetic screen isolating defects in gland cell migration has been completed and 60 alleles have been isolated that display gland cell under-migration or over-migration defects. Previous work has determined that the FGFR pathway, egl-15, and the integrin receptor pathway, ina-1, provide a migratory stop cue during gland cell migration. Despite extensive efforts using candidate approaches, identification of downstream components to these receptors during gland migration have been unsuccessful. Loss of function mutations in a gene called cam-1 display a gland cell under-migration phenotype. The CAM-1 protein is a ROR tyrosine kinase receptor that binds the Wnt ligand and induces a kinase-dependent response to provide a positive cue for gland migration. The forward genetic screen has identified several strains with Cam-1-like gland cell under-migration phenotypes as well as Egl-15 and Ina-1-like over-migration defects. Preliminary mapping of two strains that display penetrant under-migration defects have isolated two alleles to chromosome locations distinct from known cam-1 pathway components. Further mapping studies, whole genome sequencing and genetic epistasis will be used to define the genetic pathways regulating gland cell migration during pharynx development.