Patterning of sexually dimorphic neurogenesis in the caenorhabditis elegans ventral cord by Hox and TALE homeodomain transcription factors.

BACKGROUND: Reproduction in animals requires development of distinct neurons in each sex. In C. elegans, most ventral cord neurons (VCNs) are present in both sexes, with the exception of six hermaphrodite-specific neurons (VCs) and nine pairs of male-specific neurons (CAs and CPs) that arise from analogous precursor cells. How are the activities of sexual regulators and mediators of neuronal survival, division, and fate coordinated to generate sex-specificity in VCNs? RESULTS: To address this, we have developed a toolkit of VCN markers that allows us to examine sex-specific neurogenesis, asymmetric fates of daughters of a neuroblast division, and regional specification on the anteroposterior axis. Here, we describe the roles of the Hox transcription factors LIN-39 and MAB-5 in promoting survival, differentiation, and regionalization of VCNs. We also find that the TALE class homeodomain proteins CEH-20 and UNC-62 contribute to specification of neurotransmitter fate in males. Furthermore, we identify that VCN sex is determined during the L1 larval stage. CONCLUSIONS: These findings, combined with future analyses made possible by the suite of VCN markers described here, will elucidate how Hox-mediated cell fate decisions and sex determination intersect to influence development of neuronal sex differences.

Somatic sexual differentiation in Caenorhabditis elegans.

The two sexes of the nematode Caenorhabditis elegans are the self-fertile hermaphrodite (essentially a female with a mixed germ line) and the male, and these differ extensively in anatomy, physiology, and behavior. At hatching, C. elegans larvae of each sex are nearly indistinguishable, differing mainly in the sex-specific death of a handful of neurons. After birth, however, a number of blast cells undergo radically different lineages and differentiation programs in the two sexes, leading to adults in which about one-third of cells are overtly dimorphic. The first C. elegans mutants causing discordance between genetic and phenotypic sex were isolated more than 30 years ago. Since then much progress has been made in uncovering the chromosomal elements and downstream regulatory pathways that control sex determination and sexual differentiation in the worm. The primary signal for sex determination is the ratio of X chromosomes to sets of autosomes, with hermaphrodites normally having two X chromosomes (XX) and males one (XO). The X:A signal is exquisitely dose-sensitive and operates via a group of X-linked regulators acting in opposition to a group of autosomal regulators that compete for the control of the master sex regulator xol-1. The activity of xol-1 coordinately regulates the formation of an active X chromosome dosage compensation complex and the activity of a sex determination regulatory cascade. The sex determination pathway globally controls all sexually dimorphic features by conferring sex specificity on downstream regulatory modules, largely via the action of TRA-1, a Ci/GLI family transcription factor with high activity in hermaphrodites and low activity in males. Much of this regulation involves the imposition of sex-specific activity on general developmental regulators in specific cell lineages. Recent work has answered long-standing questions about the molecular mechanisms controlling the sex determination pathway and shown that some C. elegans sexual regulators have counterparts regulating sexual development in other phyla.