Sexually dimorphic neurogenesis in C. elegans depends on the coordinated activities of Hox transcription factors and the sex-determination cascade culminating in the transcription factor TRA-1. The hermaphrodite VC motor neurons, which regulate egg laying, and the male CA and CP motor neurons, which innervate mating muscles, arise from analogous precursor cells (Pn.aap), yet adopt unique targets, neurotransmitter expression, and morphology. A striking sexual dimorphism in this lineage is the male-specific cell division of P3.aap-P8.aap, each of which generates a CA neuron that expresses the peptidergic marker
ida-1::gfp and a CP neuron that expresses the serotonergic marker
tph-1::gfp. In males, one of two Hox proteins, LIN-39 or MAB-5, must be present to promote this division, and LIN-39 is additionally required to specify serotonergic fate in CP.1 In hermaphrodites, P3.aap-P8.aap do not divide, but require LIN-39 to survive and differentiate into VCs.2 While it is clear that motor neuron specification is sexually dimorphic, it is not known how LIN-39 and MAB-5 interact with TRA-1 to generate CAs and CPs in males, but VCs in hermaphrodites. We hypothesize that the asymmetric CA/CP neurogenic division is promoted in males by LIN-39 and MAB-5. In hermaphrodites, TRA-1 opposes this Hox-mediated division to promote VC motor neuron fate. To test our hypothesis, we seek genes whose loss of function disrupts this division. We predict that these genes will include cofactors of LIN-39 and MAB-5 that promote asymmetric neuronal division and targets of TRA-1 that make this division sex-specific. In a pilot RNAi screen, we have found that the Hox gene
nob-1 is required with
mab-5 and
lin-39 for male-specific neurogenesis in the Pn.aap lineage.
nob-1(RNAi) males fail to express
tph-1::gfp in CPs, but do express
ida-1::gfp, suggesting that CAs are present. Previous work has shown that
nob-1 is required for the asymmetric division of the hypodermal cell T.3 Our preliminary results suggest that
nob-1 may similarly promote the asymmetric division that differentiates CP from CA. We are exploring interactions among
nob-1,
lin-39, and
mab-5, as well as the roles of other
nob-1-interacting genes, such as
psa-3/Meis and Wnt pathway components, in promoting asymmetric neuronal division in males. We continue to seek additional regulators of the CA/CP generating division in a genetic screen. Studying these regulators will elucidate how Hox-mediated patterning intersects with sexual regulation to specify neurons that control sexually dimorphic behavior. 1Salser, SJ, et al., Genes & Development 7:1714-1724; 2Clark, SG, et al. Cell 74: 43-55; 3Arata, Y., et al. Developmental Cell 11: 105-115.