Genetic screen for small body size mutants in C. elegans reveals many TGFβ pathway components

Abstract

In the nematode Caenorhabditis elegans, a TGFbeta-related signaling pathway regulates body size and male tail morphogenesis. We sought to identify genes encoding components or modifiers of this pathway in a large-scale genetic screen. Remarkably, this screen was able to identify essentially all core components of the TGFbeta signaling pathway. Among 34 Small mutants, many mutations disrupt genes encoding recognizable components of the TGFbeta pathway: DBL-1 ligand, DAF-4 type II receptor, SMA-6 type I receptor, and SMA-2, SMA-3, and SMA-4 Smads. Moreover, we find that at least 11 additional complementation groups can mutate to the Small phenotype. Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. Two genes, sma-11 and sma-20, also influence regulation of the developmentally arrested dauer larval stage, suggesting a role in a second characterized TGFbeta pathway in C. elegans. Other genes may represent tissue-specific factors or parallel pathways for body size control. Because of the conservation of TGFbeta signaling pathways, homologs of these genes may be involved in tissue specificity and/or crosstalk of TGFbeta pathways in other animals.

mab-2encodes RNT-1, aC. elegansRunx homologue essential for controlling cell proliferation in a stem cell-like developmental lineage

“…Moreover, we can see no phenotypic similarities between rnt-1 and Sma male tails. The Sma phenotype is typified by fused rays (Hodgkin, 1983;Morita et al, 1999;Savage-Dunn et al, 2003), whereas the rnt-1 phenotype is typified by missing rays caused by failures in seam cell proliferation, as indicated by our lineage analysis. It is possible that rnt-1 has some minor downstream role in ray morphogenesis, as evidenced by the very low penetrance ray fusion phenotype we observe in rnt-1 animals, but it is certain that the major focus of rnt-1 action is in the regulation of seam cell proliferation.…”

TheCaenorhabditis elegans schnurrihomologsma-9mediates stage- and cell type-specific responses to DBL-1 BMP-related signaling

“…LG X, sma-9(wk55, wk62, wk71, wk82) (Savage-Dunn et al, 2003); sma-9(bx120), lon-2(e678), dbl-1(ctIs40) (Suzuki et al, 1999); cat-2::gfp complex extrachomosomal arrays bxEx44, bxEx45, bxEx46 and bxEx47 (Lints and Emmons, 1999); and mnIs17, an integrated derivative of osm-6::gfp array mnEx64 (Collet et al, 1998).…”

“…The isolation of wk and bx alleles was described previously (Savage-Dunn et al, 2003;Lints and Emmons, 2002). The qc alleles were isolated in a non-complementation screen.…”

“…From a screen of approximately 4000 F1 cross progeny, nine new alleles of sma-9 were isolated. Mapping sma-9 was previously mapped to linkage group X (Savage-Dunn et al, 2003). This map position was refined using SNP markers.…”

“…To identify additional components of the DBL-1 pathway and in particular those that confer specific pathway responses, we performed forward genetic screens for additional mutations affecting body size or male sensory ray patterning (Savage-Dunn et al, 2003;Lints and Emmons, 2002). Here we report the isolation of the C. elegans shn homolog sma-9, and provide the first evidence of a conserved role for Shn proteins in BMP-related signaling.…”