The major genes that control sexual cell fate decisions in the worm are genetically well-characterised. All of these genes have now been cloned and the present challenge is to elucidate the molecular mechanisms that underlie the genetic pathway. I have been focusing on the role of
tra-2 in regulating sexual cell fate. Here, I present evidence for a direct interaction between TRA-2A and HER-1. See abstract by Spence et al. for details about other interactions involving
tra-2.
tra-2 promotes female development in XX animals. I have shown that a predicted membrane protein, TRA-2A, provides the primary somatic feminising activity of the
tra-2 locus (1,2). It has been hypothesised that the predicted HER-1 protein is secreted (3) and binds to and inactivates TRA-2A in XO males. Thus, TRA-2A and HER-1 regulate sexual cell fates by mediating cell-to-cell signalling. This model strongly predicts that if TRA-2A escapes negative regulation by HER-1, then an XO animal will be transformed from male to hermaphrodite. I have shown that heat shock driven expression of TRA-2A is sufficient to completely transform an XO animal from male to fertile hermaphrodite (2). Presumably this occurs because TRA-2A titrates HER-1 activity. I have also characterised a novel class of
tra-2(eg) for (enhanced gain-of-function) feminising mutations. XX
tra-2(eg) mutants are completely hermaphrodite, whereas XO
tra-2(eg) mutants are sexually transformed from male to hermaphrodite. The molecular and genetic properties of the
tra-2(eg) mutations indicate that they are likely to identify a potential TRA-2A/HER-1 interaction site. Analysis of XO
tra-2(eg) mutants has also led to the speculation that an interaction exists between the sex determination and dosage compensation pathways. Finally, I am analysing potential interactions between TRA-2A and HER-1 at the biochemical level by expressing these proteins in a variety of heterologous expression systems.