The Caenorhabditis elegans pharynx, or foregut, is used as a model organ to study morphogenesis during development. Its pharyngeal gland cells support a secretory and lubricating function in the digestive tract. The
g1P gland cell has a cellular extension that spans most of the length of the pharynx. Of particular interest is how the
g1P cell migrates through the organ and forms this extension. During embryonic development, the cell uses retrograde extension: part of the cell remains anchored at its origin in the anterior aspect of the pharynx and leaves a cellular projection in its migratory wake. The molecular pathway controlling this migration is not well understood, and appears to be genetically distinct from dendrite and glial extension in amphid neurons, which require
dex-1 and
dyf-7 to anchor their extensions (1).
cam-1 is the exclusive C. elegans Receptor tyrosine kinase-like Orphan Receptor (ROR), functioning as a non-canonical Wnt receptor. Deficiencies in this gene result in an under-migrated
g1P, where the cell body stops prematurely in an anterior position. While RORs can be exclusive to nervous system development (sea slug and Drosophila),
cam-1 functions in multiple organs and tissues during C. elegans embryonic development, similar to vertebrate RORs. Differing from vertebrates, however, is requirement of the kinase domain for full ROR developmental functioning in the worm (2, 3). Down stream effectors of the kinase specific function are not well understood. To better understand the retrograde extension mechanism and identify components of the
cam-1 pathway, a forward genetic screen was conducted. A
phat-1::YFP strain was mutagenized with EMS, and 4,986 individual strains were screened for gland cell displacement. 60 strains with aberrant
g1P position were isolated; 24 of these displayed an under-migration similar to
cam-1 loss-of-function mutations. A subset of these 24 are homozygous viable and were selected for preliminary genetic mapping. Six alleles have been mapped to chromosome IV with two complementation groups. In collaboration with the C. elegans Gene Knockout Consortium, we are identifying the causative mutations through whole genome sequencing. One complementation group is likely
cwn-2, and the other
ham-1. (1) Heiman and Shaham, 2009. Cell 137:344-355. (2) Bainbridge et al., 2015. PLoS One 9:
e102695. (3) Chien et al., 2015. Dev Biol 404:55-65.