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.

A Sex Determining Hermone?

Craig Hunter, Marc Perry and Bill Wood

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.