title: Sexually Dimorphic Differentiation of a C. elegans Hub Neuron Is Cell Autonomously Controlled by a Conserved Transcription Factor.
abstract: Functional and anatomical sexual dimorphisms in the brain are either the result of cells that are generated only in one sex or a manifestation of sex-specific differentiation of neurons present in both sexes. The PHC neuron pair of the nematode C. elegans differentiates in a strikingly sex-specific manner. In hermaphrodites the PHC neurons display a canonical pattern of synaptic connectivity similar to that of other sensory neurons, but in males PHC differentiates into a densely connected hub sensory neuron/interneuron, integrating a large number of male-specific synaptic inputs and conveying them to both male-specific and sex-shared circuitry. We show that the differentiation into such a hub neuron involves the sex-specific scaling of several components of the synaptic vesicle machinery, including the vesicular glutamate transporter eat-4/VGLUT, induction of neuropeptide expression, changes in axonal projection morphology, and a switch in neuronal function. We demonstrate that these molecular and anatomical remodeling events are controlled cell autonomously by the phylogenetically conserved Doublesex homolog dmd-3, which is both required and sufficient for sex-specific PHC differentiation. Cellular specificity of dmd-3 action is ensured by its collaboration with non-sex-specific terminal selector-type transcription factors, whereas the sex specificity of dmd-3 action is ensured by the hermaphrodite-specific transcriptional master regulator of hermaphroditic cell identity tra-1, which represses the transcription of dmd-3 in hermaphrodite PHC. Taken together, our studies provide mechanistic insights into how neurons are specified in a sexually dimorphic manner.
authors.affiliation: Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, NY 10027, USA. Electronic address: es2754@columbia.edu.
authors.forename: Esther
authors.initials: E
authors.lastname: Serrano-Saiz
authors.affiliation: Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, NY 10027, USA.
authors.forename: Meital
authors.initials: M
authors.lastname: Oren-Suissa
authors.affiliation: Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, NY 10027, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Bayer
authors.affiliation: Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, NY 10027, USA. Electronic address: or38@columbia.edu.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D012727:Sex Characteristics; D012733:Sex Differentiation; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors