Our lab is investigating genes that regulate the actin-mediated cell shape changes that drive C.elegans embryonic elongation.
let-502 encodes a Rho-dependent kinase and strong antimorphic mutations display early larval arrest due to failed elongation1. We recently isolated hypomorphic homozygous viable
let-502 mutations. Some of these alleles sufficiently decrease maternal expression to reveal a new, early embryonic phenotype. The embryos either do not complete any cell cleavages or form cleavage furrows that regress and result in multinucleated embryos. Some of these embryos also show defects in asymmetry, some appear larger than wild-type embryos and this may indicate defects in oocyte formation. Consistent with a role in cleavage furrow formation, LET-502 localizes to the furrow during early cell divisions.
mel-11 encodes a myosin phosphatase and suppresses
let-502 elongation defects1,2. A hypomorphic
mel-11 mutant also suppresses the cleavage defects caused by
let-502 mutants suggesting that
mel-11 also may play a role in cytokinesis. However, these
mel-11 mutant embryos do not show cleavage defects on their own.
mlc-4 encodes a nonmuscle regulatory light chain and is a downstream target for both
let-502 and
mel-11 in embryonic elongation.
mlc-4 previously has been shown to play a role in early cleavage3. Together, these results suggest that the pathway regulating embryonic elongation may be similar to the pathway regulating early cleavage. In higher eukaryotes nonmuscle myosin, Rho, RhoGEF and the Rho-binding kinase effector, Citron-kinase, have been shown to regulate cytokinesis and cleavage furrow formation. Since the predicted C. elegans homologue for Citron has no associated kinase domain, in C. elegans LET-502 could be the kinase required for early cleavage.
let-502's role in cytokinesis is currently being investigated using various molecular and genetic tools. Wissmann, A., J. Ingles, J.D. McGhee and P.E. Mains, 1997. Genes Dev. 11:409-422. Wissmann, A., J. Ingles and P.E. Mains, 1999. Develop. Biol. 209:111-127. Shelton, C. A., J.C. Carter, G.C. Ellis and B. Bowerman, 1999. J. Cell. Biol. 146: 439-451.