Worm Breeder's Gazette 13(2): 38 (February 1, 1994)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
daf-4 , sma-2 , sma-3 ,and sma-4 mutants show two phenotypes in common: small body size (Sma) and specific male tail ray and spicule defects (Mab). daf-4 has recently been shown to encode a serine/threonine kinase receptor that binds human BMP-2 ,a TGF-ß-like ligand (Estevez et al., Nature 365: 644). The striking similarity in mutant phenotypes therefore implicates sma-2 , sma-3 ,and sma-4 in this TGF-ß-ike signal transduction pathway. We wondered whether other known genes could also be involved in TGF-ß-like signalling and whether they could be used to place daf-4 , sma-2 , sma-3 ,and sma-4 into an ordered genetic pathway. We began by examining the phenotypes of double mutants between these four genes and lon-1 , lon-2 ,and lon-3 .The Lon phenotype of lon-1 is epistatic to all of the Sma phenotypes, while the Sma phenotypes of daf-4 , sma-2 , sma-3 ,and sma-4 are epistatic to the Lon phenotypes of lon-2 and lon-3 :
In most instances, the lon genes did not affect the other phenotypes of these mutants (Mab and, for daf-4 ,dauer constitutive, Daf-c). We did, however, notice one interesting exception: lon-2 enhances maternal rescue of the daf-4 Daf-c phenotypes. In particular, the daf-4 ; lon-2 progeny of heterozygous ( daf-4 /+; lon-2 /+)mothers were more likely to develop into adults (10% of F2 progeny became Sma adults) than were the daf-4 progeny of daf-4 /+mothers (2% of F2 progeny were Sma adults). This suppression requires maternal daf-4 product, since all of the progeny of daf-4 ;10n-2Sma adults enter dauer at 25°C. This result strengthens the link between lon-2 and this signalling pathway, leading us to propose that lon-2 is a negative regulator of daf-4 activity. For example, lon-2 could encode an antagonistic ligand that forms heterodimers with an activating ligand for daf-4 ,or it could encode a component of the extracellular matrix that binds the ligand for daf-4 and restricts its access to the receptor.
Alternatively, these genetic interactions could be the result of less specific effects of the mutant proteins. One additional observation, however, demonstrates that a Lon phenotype can be caused by over-activation of this pathway. Clones that rescue sma-4 in transgenic animals often confer a Lon phenotype. Taken together, these results suggest that at least a subset of the lon genes, most likely including lon-2 ,may be involved in this TGF-ß-like signalling pathway. Further testing of these hypotheses will require the identification of null alleles for these genes and the molecular cloning of their gene products.