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Elife. 2019 Jan 1;8. pii: e42078. doi: 10.7554/eLife.42078.

Timing mechanism of sexually dimorphic nervous system differentiation.

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Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States.
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Department of Biology, University of Rochester, Rochester, United States.
DelMonte Institute for Neuroscience, Department of Biomedical Genetics, University of Rochester, New York, United States.


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.


C. elegans; gene regulation; genetics; neuroscience; sexual differentiation

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