Cell shape in animals is determined by a complex network of interactions between extracellular components such as the extracellular matrix and the internal cytoskeleton. Linkage occurs via integral membrane proteins. Both external cues, and the cellular differentiation state, determine the specific response of a given cell in regulating its shape. The hypodermal cells in C.elegans undergo a dramatic change in cell shape during morphogenesis of the embryo. Priess & Hirsh proposed that this shape change results from hypodermal actin fiber-dependent contraction that increases internal pressure within the embryo, squeezing an elliptical ball of cells (the embryo) into a long tube (the worm)[1]. We identified a zygotic lethal mutation (ca201) defective in elongation. This mutation leads to arrest during early morphogenesis but does not affect later stage differentiation markers such as pharyngeal and gut development and cuticle formation. ca201 was shown to be an allele of the previously identified gene let-502 isolated in a saturation screen for lethals within LGI left by Howell & Rose[2] (thank you, Ann, for kindly supplying the other five let-502 alleles to us). The let-502 cDNA was cloned and the let-502 mutations were identified (see abstract by Julia Ingles et al.). Sequence analysis reveals that LET-502 is a member of a new family of serine/threonine kinases that include p160ROCK, ROK , Rho-kinase and human myotonic dystrophy kinase. p160ROCK, ROK and Rho-kinase have been shown to bind the Ras-related GTP-binding protein Rho and a sequence comparison suggests that this is also the case for LET-502. Furthermore, a PH-domain and a Cysteine rich region similar to that found in Protein Kinase C have been identified. A let-502/lacZ fusion expresses in hypodermal cells and especially in the lateral seam cells, where the most dramatic cell shape changes take place during morphogenesis. A limited screen for suppressors of ca201 embryonic lethality identified two alleles within one gene (tentatively named kis-1 for kinase suppressor). Both alleles suppress ca201 to sterile adults. When separated from ca201, one allele (sb55) is fertile, whereas the other (sb56) gives sterile adults. sb56 has now been mapped and rescued and encodes part of a phosphatase complex. A model showing how this set of genes might be related to the observed cell shape changes will be presented. 1 Priess, J.R. & Hirsh, D.L. Developmental Biology 117, 156-173 (1986) 2 Howell, A.M. & Rose, A.M. Genetics 126, 583-592 (1990)

Affiliation:
- Dept. of Medical Biochemistry University of Calgary Calgary, Alberta T2N 4N1 Canada