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.