The pattern of cell adhesions made by an organism during embryonic development is of fundamental importance in determining the final product. In C. elegans, the gonad provides us with a model to study the molecules involved in attachment of an organ to the extracellular matrix during embryonic development. Recessive mutations in
mig-4 (III) disrupt adhesion of the gonad primordium to its substrate within embryos and early L1 larvae. In addition, the pharynx in
mig-4 mutants is misaligned and the M mesoblast is unattached.
mig-4 (
rh51) has been mapped between
vab-7 and the right hand breakpoint nDf40 between cosmids M142 and K01G5 on the physical map. Recently, we rescued
mig-4 (
rh51) by microinjection of cosmid M142. Moreover, an HindIII RFLP was found in genomic DNA from a
mig-4 gamma allele (
rh269) probed with cosmid M142. Our candidate molecule, M142.2, is a 500 aa predicted protein with the hallmarks of extracellular matrix proteins. Namely, it is a secreted protein with von Willebrand type A (vWF-A) domains and a
cut-1 like domain. The vWF-A domain is found in many extracellular proteins known to be involved in cell adhesion and migration. The
cut-1 region is found, thus far, only in proteins of the specialized cuticular extracellular matrix. Overall, the
mig-4 candidate protein may act as an adaptor molecule binding a larger molecule to the matrix itself or to a cell surface receptor. We are currently subcloning M142 to confirm that M142.2 is indeed
mig-4. Further work will involve defining the molecular nature of the mutations in our
mig-4 mutant collection as a confirmation of the cloning of
mig-4 as well as determining the expression pattern of MIG-4 using GFP chimeras.