Sexually Dimorphic unc-6/Netrin Expression Controls Sex-Specific Maintenance of Synaptic Connectivity

Peter Weinberg, Matthew Berkseth, David Zarkower, Oliver Hobert

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Nervous systems display intriguing patterns of sexual dimorphisms across the animal kingdom, but the mechanisms that generate such dimorphisms remain poorly characterized. In the nematode Caenorhabditis elegans, a number of neurons present in both sexes are synaptically connected to one another in a sexually dimorphic manner as a result of sex-specific synaptic pruning and maintenance [1–3]. We define here a mechanism for the male-specific maintenance of the synaptic connections of the phasmid sensory neuron PHB and its male-specific target, the sex-shared AVG interneuron. We show that the C. elegans Netrin ortholog UNC-6, signaling through its cognate receptor UNC-40/DCC and the CED-5/DOCK180 guanine nucleotide exchange factor, is both required and sufficient for male-specific synaptic maintenance. The dimorphism of unc-6 activity is brought about by sex-specific regulation of unc-6 transcription. Although unc-6 is transcribed in the AVG neuron of males and hermaphrodites during juvenile stages, unc-6 expression is downregulated in AVG in hermaphrodites during sexual maturation but is maintained during sexual maturation of males. unc-6 downregulation in hermaphrodites is conferred by the master regulator of hermaphrodite sexual identity, the Gli/CI homolog TRA-1, which antagonizes the non-sex-specific function of the LIM homeobox gene lin-11, a terminal selector and activator of unc-6 in AVG. Preventing the downregulation of unc-6 in AVG of hermaphrodites through ectopic expression of unc-6 in transgenic animals results in the maintenance of the PHB>AVG synapses in hermaphrodites. Taken together, intersectional transcriptional regulation of unc-6/Netrin is required and sufficient to cell autonomously pattern sexually dimorphic synapses. Weinberg et al. show that the unc-6/Netrin system is required and sufficient to maintain male-specific synaptic connectivity of two sex-shared neurons. Sex specificity of unc-6 function is ensured by sex-specific transcription of unc-6 via a sex-specific transcription factor collaborating with a cell-specific terminal selector of neuronal identity.

Original languageEnglish (US)
Pages (from-to)623-629.e3
JournalCurrent Biology
Volume28
Issue number4
DOIs
StatePublished - Feb 19 2018

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Keywords

  • C. elegans
  • Netrin
  • sexual dimorphisms
  • transcriptional regulation

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