Worm Breeder's Gazette 13(5): 48 (February 1, 1995)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

unc-40 Encodes a Protein Related to the Human DCC (Deleted Colorectal Cancer) Protein.

Shirley Chan1, Ming-Wan Su1, Joe Culotti1, Ed Hedgecock2

1 Samuel Lunenfeld Research Institute of Mt. Sinai Hospital Toronto, Canada
2 Department of Biology Johns Hopkins University Baltimore, MD

unc-40 is required for circumferential pioneer migrations
of axon growth cones and mesodermal cells on the basal surface
of the epidermis of C. elegans. Although unc-40 mutations
primarily affect migrations oriented towards the ventral
side, they also affect dorsally-oriented migrations
(although to a lesser extent). The unc-40 gene was cloned
by mapping unc-40 mutations relative to DNA polymorphisms
followed by transformation rescue. We have determined
what we believe may be the entire coding region of this gene
comprising 4 kb of sequence. From amino to carboxy terminus,
the predicted UNC40 protein has 4 immunoglobulin domains,
6 fibronectin type III domains, a single transmembrane
domain and an intracellular domain of 309 amino acids.
The overall domain structure of the predicted UNC-40 protein
is very similar to the human DCC (deleted colorectal cancer)
protein which was initially (incorrectly?) implicated
in a fraction of human colorectal cancers. More recently,
a DCC-related gene has been cloned from chicken (Jost Vielmetter
and William Dryer, Cal Tech, personal communication)
called neogenin. neogenin is not the chicken DCC gene,
but is related to it.
The fibronectin and immunoglobulin domains of UNC-40
are clearly more related to DCC and Neogenin than they are
to similar domains in other proteins. Interestingly,
the Neogenin protein is expressed in neurons as they extend
axons in the developing chick nervous system. We are currently
attempting several methods for examining the expression
pattern of the UNC-40 protein.