SMA-3 Smad has specific and critical functions in DBL-1/SMA-6 TGF beta-related signaling

A TGF beta signal transduction cascade controls body size and male tail mor phogenesis in the nematode Caenorhabditis elegans. We have analyzed the fun ction of the sma-3 Smad gene, one of three Smad genes that function in this pathway. Null mutations in sma-3 are at least as severe as null mutations in the ligand and type I receptor genes, dbl-1 and sma-6, indicating that t he other Smads do not function in the absence of SMA-3. Furthermore, null m utations in sma-3 do not cause defects in egg laying or in regulation of th e developmentally arrested dauer larva stage, indicating no overlapping fun ction with another C. elegans TGF beta signaling pathway. The sma-3 gene is widely expressed at all developmental stages in hermaphrodites and males. The molecular lesions associated with eight sma-3 alleles of varying severi ty have been determined. The missense mutations cluster in two previously i dentified regions important for Smad function. (C) 2000 Academic Press.