mab-3 is a direct tra-1 target gene regulating diverse aspects of C-elegans male sexual development and behavior

Sex determination is controlled by global regulatory genes, such as tra-l i n Caenorhabditis elegans, Sex lethal in Drosophila, or Sry in mammals, How these genes coordinate sexual differentiation throughout the body is a key unanswered question, tra-1 encodes a zinc finger transcription factor, TRA- 1A, that regulates, directly or indirectly, all genes required for sexual d evelopment, mab-3 (male abnormal 3), acts downstream of tra-l and is known to be required for sexual differentiation of at least two tissues, mab-3 di rectly regulates yolk protein transcription in the intestine and specifies male sense organ differentiation in the nervous system. It encodes a transc ription factor related to the products of the Drosophila sexual regulator d oublesex (dsx), which also regulates yolk protein transcription and male se nse-organ differentiation. The similarities between mab-3 and dsx led us to suggest that some aspects of sex determination may be evolutionarily conse rved. Here we find that mab-3 is also required for expression of male-speci fic genes in sensory neurons of the head and tail and for male interaction with hermaphrodites. These roles in male development and behavior suggest f urther functional similarity to dsx, In male sensory ray differentiation we find that MAB-3 acts synergistically with LIN-32, a neurogenic bHLH transc ription factor. Expression of LIN-32 is spatially restricted by the combine d action of the Hox gene mab-5 and the hairy homolog lin-22, while MAB-3 is expressed throughout the lateral hypodermis, Finally, we find that mab-3 t ranscription is directly regulated in the intestine by TRA-1A, providing a molecular link between the global regulatory pathway and terminal sexual di fferentiation.