Worm Breeder's Gazette 11(4): 86
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.
We have extended our initial analysis of her-1 genetic mosaics (WBG 11(2) 1990) by monitoring losses of the her-1(+) duplications using unc-42, ge markers and by following the duplication cytologically in the germline. The phenotypes of XO her-1 mosaics are variable, but in general they indicate that her-1 can function non-cell autonomously in that the her- 1 genotype of P1-derived cells can influence the sexual phenotype of AB-derived cells. Specifically, her-1(+) (male) P1 cells can masculinize her-1(+) (hermaphrodite) AB-derived cells, while her-1(-) ( hermaphrodite) P1-derived cells can feminize her-1(+) (male) AB- derived cells. We found no evidence for the converse influence of AB her-1 genotype on sexual differentiation of P1-derived cells. Our concomitant molecular characterization of the her-1 gene suggests an attractive explanation for the genetic observations. Sequence analysis of PCR-generated her-1 cDNAs specific for the larger rare transcript (WBG 11(2) 1990) reveals a potential long ORF which is spliced in-frame across all three splice-junctions and encodes a generally hydrophilic 20 kD protein with a 16-residue hydrophobic signal sequence on its N-terminus. Thus a product of the her-1 gene is likely to be a secreted, diffusible polypeptide. Interestingly, P. Kuwabara and J. Kimble (CSH Meeting Abstracts, 1989 and personal communication) have found that the longest tra-2 mRNA could encode a large protein with both a putative signal sequence and a hydrophobic trans-membrane domain (but no significant homology to any known proteins). The tra-2 gene appears to be expressed in both XX and XO animals (Okkema and Kimble, CSH Meeting Abstracts, 1989), whereas her- 1 appears to be expressed only in XO animals (Trent et al., CSH Meeting Abstracts, 1989). We propose that in XO animals the her-1 secreted peptide binds to and inhibits function of the putative tra-2 transmembrane receptor present on both AB- and P1-derived cells. In the her-1 mosaics with her-1(+) P1-derived cells and her-1(-) AB derived cells, the diffusible her-1 ligand produced by P1 descendants masculinizes both P1- and some AB-derived cells. In the her-1 mosaics with her-1(-) P1- derived cells and her-1(+) AB-derived cells, the her-1 ligand produced by AB descendants is insufficient to bind to all the tra-2 receptors on both AB- and P1-derived cells so that the tra-2 receptors on P1 descendants effectively feminize AB-derived cells by titrating the her- 1 ligand. This apparent absence of influence of AB genotype on sexual differentiation of P1 descendants, could be explained if P1-derived cells produce more tra-2 receptors (or her-1 ligand) than AB-derived cells; for example, free tra-2 receptors on the latter would not be sufficient to titrate her-1 ligand from P1 descendants to the point of masculinizing P1 derived cells. Furthermore, if tra-2 is expressed at a higher level in XX animals than in XO animals, then this model could explain the puzzling results of Villeneuve and Meyer (Genetics 124; 91- 114,1990) for genetic mosaic analysis of sdc-1. XX animals genetically mosaic for sdc-1 are almost always wild-type hermaphrodites displaying no masculinization. Since sdc-1 represses her-1 transcription (Trent, et al. submitted) her-1 would be expressed in some cells of these animals, but at levels that could be insufficient to masculinize any tissue if tra-2 is expressed at a higher level in XX animals than in XO animals. We note finally that her-1 could act to reset the sex determination pathway in XO animals for cells that mis-read their X/A ratio. If such a cell should follow a hermaphrodite fate, that animal could develop as an abnormal male unable to mate. Secretion of the her-1 ligand by neighboring cells would reset the sex determination pathway in the wayward cell(s) so that all cells follow male fates. A non- autonomous sex-determination step might have evolved in males because of the greater complexity of male development.