GASTRULATION INITIATION IN CAENORHABDITIS-ELEGANS REQUIRES THE FUNCTION OF GAD-1, WHICH ENCODES A PROTEIN WITH WD REPEATS

Gastrulation in Caenorhabditis elegans is normally initiated by inward migration of the two gut precursor (E) cells at the 26-cell stage. A strong loss-of-function, temperature-sensitive, embryonic lethal mutat ion in the maternally required gene gad-1 (gastrulation defective) pre vents gastrulation initiation. In embryos from homozygous mutant gad-1 (ct226) hermaphrodites reared at 25 degrees C, the E cells divide ear ly with abnormal spindle orientations and fail to migrate into the emb ryo, and no subsequent gastrulation movements occur. These embryos con tinue to develop and differentiate the major cell types, but they unde rgo little morphogenesis. The temperature-sensitive period of the muta nt is during early embryogenesis, prior to gastrulation onset. The pre dicted translation product of the cloned gad-1 gene includes six P-tra nsducin-related repeats of the WD motif, which has been implicated in protein-protein interactions. The ct226 mutation alters a conserved re sidue in one of these repeats. Injection of gad-1 antisense RNA into w ild-type hermaphrodites mimics the mutant phenotype in progeny embryos . We conclude that the gad-1 gene product is required for initiation o f gastrulation in C. elegans. (C) 1998 Academic Press.