Worm Breeder's Gazette 13(2): 76 (February 1, 1994)
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.
Cadherins were originally defined as a group of small (~130kd) transmembrane proteins that mediate Ca(2+)-dependent cell-cell adhesion. These so-called "classical" cadherins have a highly conserved primary structure consisting of a large extracellular domain and a relatively small cytoplasmic domain. The extracellular domain consists of five homologous subdomains of approximately 100 amino acids each. These subdomains have been termed cadherin domains. Several other recently isolated proteins containing cadherin domains have structures divergent from the classical cadherins, indicating a cadherin superfamily. In Drosophila there are at least two members of the superfamily; both are large putative transmembrane proteins containing many tandem cadherin domains. The best characterized of the two is the fat gene product, which contains 34 cadherin domains, four EGF-like repeats and a unique cytoplasmic domain. It is not yet known whether this protein functions as a cell adhesion molecule; however, recessive lethal mutations in this gene result in hyperplastic growth of the larval imaginal discs and alterations in disc morphology.
We have been characterizing three genes in C. elegans that contain cadherin domains. Two of these genes were isolated in Los Angeles using a degenerate PCR approach and the third was sequenced by the Sequencing Consortium. In Boulder, we have found that all three cdh (cadherin-related) genes produce transcripts of approximately 11 kb, and since this is nearly as large as the fat transcript it is likely that they encode proteins containing many cadherin domains. These transcripts are present in embryos undergoing morphogenesis and, at a lower level, in L1 larvae. The only member of this set so far sequenced is cdh-3 ,which is predicted to encode a gene product that contains 18 cadherin domains, a cysteine-rich domain, a transmembrane domain and a unique, short cytoplasmic domain. We have made a lac-Z construct containing 5 kb of promoter sequence from cdh-3 (pCD L1C5 )in order to ask where this gene is transcribed. When transformed lines containing this construct are stained with X-gal, comma-stage to 3-fold-stage embryos exhibit nuclear staining in all ten seam cells and in a few anterior cells which we believe may be other hypodermal cells, possibly hyp4 or hyp6 cells. Most of the staining disappears by the L1 stage, except in several cells in the head, four of which are likely to be HL, H0 R, H1 Land H1 R.Staining is not seen at any other developmental stage. In collaboration with Ronald Plasterk we are attempting to knock out cdh-3 .