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 Caenorhabditis elegans male is controlled by the temporally regulated miRNA let-7 and its target lin-41, a translational regulator. lin-41 acts through lin-29a, an isoform of a conserved Zn finger transcription factor, expressed in a subset of sex-shared neurons only in the male. Ectopic lin-29a is sufficient to impose male-specific features at earlier stages of development and in the opposite sex. The temporal, sexual and spatial specificity of lin-29a expression is controlled intersectionally through the lin-28/let-7/lin-41 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.
Highlights
The nervous systems of males and females of many animal species display anatomical and functional differences (Jazin and Cahill, 2010; McCarthy and Arnold, 2011; Portman, 2017; Yang and Shah, 2014)
As an entry point to identify the molecular mechanisms required for the correct timing of nervous system sexual maturation, we used the previously described neurotransmitter switch of the AIM interneurons (Figure 1B–D), a sex-shared neuron class that is required for mate searching behavior (Barrios et al, 2012; Pereira et al, 2015)
Like lin-29a, the male-specificity of mab-3 and dmd-3 expression in the nervous system is controlled by the tra-1 transcription factor (Figure 9E,G) the neuronal specificity of mab-3 and dmd-3 expression is, like lin-29a, controlled by neuron-type specific terminal selectors. unc42 is a terminal selector transcription factor that controls terminal differentiation of the RMD and SMD neurons (Pereira et al, 2015), and we found that mab-3 expression in these neurons fails to be induced in an unc-42 mutant background (Figure 9C)
Summary
The nervous systems of males and females of many animal species display anatomical and functional differences (Jazin and Cahill, 2010; McCarthy and Arnold, 2011; Portman, 2017; Yang and Shah, 2014). The onset of puberty in mammals is characterized by the activation of neurons in the hypothalamus that produce hormonal signals (Avendano et al, 2017). Sexual dimorphisms in the C. elegans nervous system fall into two broad types: (1) Some neurons are present only in one sex but not the opposite sex (Sulston et al, 1980; Sulston et al, 1983). These sex-specific neurons are directly involved in distinct aspects of sex-specific mating and reproductive behavior (Emmons, 2018). Dimorphic features of sexshared neurons include sex-specific synaptic wiring patterns (Jarrell et al, 2012) and sex-specific expression of signaling molecules, such as neurotransmitters, neuropeptides and chemoreceptors
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