Timing mechanism of sexually dimorphic nervous system differentiation.

Abstract

The molecular mechanisms that control the timing of sexual differentiation in the brain are poorly understood. We found that the timing of sexually dimorphic differentiation of postmitotic, sex-shared neurons in the nervous system of the <i>Caenorhabditis elegans</i> male is controlled by the temporally regulated miRNA <i>let-7</i> and its target <i>lin-41</i>, a translational regulator. <i>lin-41</i> acts through <i>lin-29a,</i> an isoform of a conserved Zn finger transcription factor, expressed in a subset of sex-shared neurons only in the male. Ectopic <i>lin-29a</i> is sufficient to impose male-specific features at earlier stages of development and in the opposite sex. The temporal, sexual and spatial specificity of <i>lin-29a</i> expression is controlled intersectionally through the <i>lin-28/let-7/lin-41</i> heterochronic pathway, sex chromosome configuration and neuron-type-specific terminal selector transcription factors. Two Doublesex-like transcription factors represent additional sex- and neuron-type specific targets of LIN-41 and are regulated in a similar intersectional manner.