RNT-1, the C. elegans homologue of mammalian RUNX transcription factors, regulates body size and male tail development

Abstract

The rnt-1 gene is the only Caenorhabditis elegans homologue of the mammalian RUNX genes. Several lines of molecular biological evidence have demonstrated that the RUNX proteins interact and cooperate with Smads, which are transforming growth factor-beta (TGF-beta) signal mediators. However, the involvement of RUNX in TGF-beta signaling has not yet been supported by any genetic evidence. The Sma/Mab TGF-beta signaling pathway in C. elegans is known to regulate body length and male tail development. The rnt-1(ok351) mutants show the characteristic phenotypes observed in mutants of the Sma/Mab pathway, namely, they have a small body size and ray defects. Moreover, RNT-1 can physically interact with SMA-4 which is one of the Smads in C. elegans, and double mutant animals containing both the rnt-1(ok351) mutation and a mutation in a known Sma/Mab pathway gene displayed synergism in the aberrant phenotypes. In addition, lon-1(e185) mutants was epistatic to rnt-1(ok351) mutants in terms of long phenotype, suggesting that lon-1 is indeed downstream target of rnt-1. Our data reveal that RNT-1 functionally cooperates with the SMA-4 proteins to regulate body size and male tail development in C. elegans.

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

“…A recent report suggests that rnt-1 functions to regulate body size and ray morphogenesis in C. elegans by interacting with components of the Sma/Mab TGF␤ signalling pathway (Ji et al, 2004). Although we do observe a small (5%) decrease in length in rnt-1 adult hermaphrodites, this is much less severe than in Sma animals.…”

TGF-β signaling in C. elegans

“…Smads, by themselves, interact poorly with DNA and complex with other transcription factors to mediate TGF-β responses (reviewed by Massagué et al, 2005; Schmierer and Hill, 2007). In C. elegans , RNT-1 (RUNX family transcription factor) has been identified as a transcription factor that physically interacts with SMA-4 Smad in vitro and is required for normal body size, as loss of RNT-1 function results in small animals (Ji et al, 2004). In mammals, RUNX transcription factors also interact with Smads (Hanai et al, 1999; Selvamurugan et al, 2004; Zhang et al, 2000).…”

An antagonistic role for theC. elegansSchnurri homolog SMA-9 in modulating TGFβ signaling during mesodermal patterning

“…We further examined this by generating double mutants between sma-9(cc604) and mutations in additional genes that appear to function in regulating body size, including lon-1(e185), two alleles of rnt-1,e1241 and ok351, and lon-2(e678) (Ji et al, 2004;Maduzia et al, 2002;Morita et al, 2002;Brenner, 1974). lon-1 and rnt-1 function downstream (Ji et al, 2004;Maduzia et al, 2002), while lon-2 is proposed to function upstream (Brenner, 1974), of the core Sma/Mab TGF␤ pathway. We found that neither of the two rnt-1 alleles suppresses the M lineage defects of sma-9, and that lon-1(e185) suppresses the M lineage defects of sma-9 at a very low penetrance (7%) ( Table 4).…”