Sensation in a Single Neuron Pair Represses Male Behavior in Hermaphrodites

Pheromones elicit innate sex-specific mating behaviors in many species. We demonstrate that in C. elegans, male-specific sexual attraction behavior is programmed in both sexes but repressed in hermaphrodites. Repression requires a single sensory neuron pair, the ASIs. To repress attraction in adults, the ASIs must be present, active, and capable of sensing the environment during development. The ASIs release TGF-β, and ASI function can be bypassed by experimental activation of TGF-β signaling. Sexual attraction in derepressed hermaphrodites requires the same sensory neurons as in males. The sexual identity of both these sensory neurons and a distinct subset of interneurons must be male to relieve repression and release attraction. TGF-β may therefore act to change connections between sensory neurons and interneurons during development to engage repression. Thus, sensation in a single sensory neuron pair during development reprograms a common neural circuit from male to female behavior.

[1]  D. Riddle,et al.  daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase , 1990, Cell.

[2]  Erik M. Jorgensen,et al.  The Sensory Circuitry for Sexual Attraction in C. elegans Males , 2007, Current Biology.

[3]  R. Plasterk,et al.  The complete family of genes encoding G proteins of Caenorhabditis elegans , 1999, Nature Genetics.

[4]  B. Dickson,et al.  A single class of olfactory neurons mediates behavioural responses to a Drosophila sex pheromone , 2007, Nature.

[5]  J. Sulston,et al.  The Caenorhabditis elegans male: postembryonic development of nongonadal structures. , 1980, Developmental biology.

[6]  Paul W. Sternberg,et al.  A Modular Library of Small Molecule Signals Regulates Social Behaviors in Caenorhabditis elegans , 2012, PLoS biology.

[7]  Cori Bargmann,et al.  Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans. , 2003, Developmental cell.

[8]  Cori Bargmann,et al.  A cyclic nucleotide-gated channel inhibits sensory axon outgrowth in larval and adult Caenorhabditis elegans: a distinct pathway for maintenance of sensory axon structure. , 1998, Development.

[9]  P. Kuwabara,et al.  Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3. , 1999, Genes & development.

[10]  Cornelia I Bargmann,et al.  Odorant Receptor Localization to Olfactory Cilia Is Mediated by ODR-4, a Novel Membrane-Associated Protein , 1998, Cell.

[11]  D. Riddle,et al.  A Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval development. , 2000, Development.

[12]  Markus Meister,et al.  Loss of Sex Discrimination and Male-Male Aggression in Mice Deficient for TRP2 , 2002, Science.

[13]  G. Ruvkun,et al.  Biosynthesis of the Caenorhabditis elegans dauer pheromone , 2009, Proceedings of the National Academy of Sciences.

[14]  Cori Bargmann,et al.  Behavioral Choice between Conflicting Alternatives Is Regulated by a Receptor Guanylyl Cyclase, GCY-28, and a Receptor Tyrosine Kinase, SCD-2, in AIA Interneurons of Caenorhabditis elegans , 2011, The Journal of Neuroscience.

[15]  J E Sulston,et al.  Neuronal cell lineages in the nematode Caenorhabditis elegans. , 1983, Cold Spring Harbor symposia on quantitative biology.

[16]  Cornelia I. Bargmann,et al.  Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes , 2011, Nature.

[17]  G. Patterson,et al.  Regulation of signaling genes by TGFβ during entry into dauer diapause in C. elegans , 2004, BMC Developmental Biology.

[18]  Soh Kohatsu,et al.  Female Contact Activates Male-Specific Interneurons that Trigger Stereotypic Courtship Behavior in Drosophila , 2011, Neuron.

[19]  G. Miesenböck,et al.  Sex-Specific Control and Tuning of the Pattern Generator for Courtship Song in Drosophila , 2008, Cell.

[20]  Wendy S. Schackwitz,et al.  Chemosensory Neurons Function in Parallel to Mediate a Pheromone Response in C. elegans , 1996, Neuron.

[21]  Dana Carroll,et al.  Gene Activation Using FLP Recombinase in C. elegans , 2008, PLoS genetics.

[22]  Yi Zheng,et al.  Differential Expression of Glutamate Receptor Subunits in the Nervous System of Caenorhabditis elegans and Their Regulation by the Homeodomain Protein UNC-42 , 2001, The Journal of Neuroscience.

[23]  J. Hildebrand,et al.  Trans-sexually grafted antennae alter pheromone-directed behaviour in a moth , 1986, Nature.

[24]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[25]  Kaveh Ashrafi,et al.  Neural and molecular dissection of a C. elegans sensory circuit that regulates fat and feeding. , 2008, Cell metabolism.

[26]  Cori Bargmann,et al.  Laser killing of cells in Caenorhabditis elegans. , 1995, Methods in cell biology.

[27]  Cori Bargmann,et al.  Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans , 1995, Cell.

[28]  A. Alfonso,et al.  The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter. , 1993, Science.

[29]  J. Sulston,et al.  The embryonic cell lineage of the nematode Caenorhabditis elegans. , 1983, Developmental biology.

[30]  P. Sternberg,et al.  A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans , 2009, Proceedings of the National Academy of Sciences.

[31]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[32]  R. K. Herman.  Introduction to sex determination , 2005 .

[33]  Evan Z. Macosko,et al.  A Hub-and-Spoke Circuit Drives Pheromone Attraction and Social Behavior in C. elegans , 2009, Nature.

[34]  P. Sengupta,et al.  The DAF-7 TGF-beta signaling pathway regulates chemosensory receptor gene expression in C. elegans. , 2002, Genes & development.

[35]  Cori Bargmann,et al.  A Putative Cyclic Nucleotide–Gated Channel Is Required for Sensory Development and Function in C. elegans , 1996, Neuron.

[36]  O. Hobert,et al.  Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans. , 2003, Journal of neurobiology.

[37]  Cornelia I Bargmann,et al.  A Distributed Chemosensory Circuit for Oxygen Preference in C. elegans , 2006, PLoS biology.

[38]  C. Dulac,et al.  A functional circuit underlying male sexual behaviour in the female mouse brain , 2007, Nature.

[39]  J. Thomas,et al.  Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. , 1993, Genetics.

[40]  Cori Bargmann,et al.  Sensory activity affects sensory axon development in C. elegans. , 1999, Development.

[41]  Paul W. Sternberg,et al.  A blend of small molecules regulates both mating and development in Caenorhabditis elegans , 2008, Nature.

[42]  Evan Z. Macosko,et al.  A huband-spoke circuit drives pheromone attraction and social behaviour in C . elegans , 2009 .

[43]  Ikue Mori,et al.  Mutations in a Cyclic Nucleotide–Gated Channel Lead to Abnormal Thermosensation and Chemosensation in C. elegans , 1996, Neuron.

[44]  D. Riddle,et al.  Control of C. elegans Larval Development by Neuronal Expression of a TGF-β Homolog , 1996, Science.

[45]  D. Chklovskii,et al.  Wiring optimization can relate neuronal structure and function. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Lesilee S. Rose,et al.  Two heteromeric kinesin complexes in chemosensory neurons and sensory cilia of Caenorhabditis elegans. , 1999, Molecular biology of the cell.

[47]  J. Hildebrand,et al.  Male moths bearing transplanted female antennae express characteristically female behaviour and central neural activity , 2010, Journal of Experimental Biology.

[48]  H. Horvitz,et al.  Caenorhabditis elegans rab-3 Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles , 1997, The Journal of Neuroscience.

[49]  J. Scholey,et al.  Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons , 2004, Nature Cell Biology.

[50]  D. Logan,et al.  Sexual dimorphism in olfactory signaling , 2010, Current Opinion in Neurobiology.

[51]  D. Riddle,et al.  The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development , 1993, Nature.