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Glia-derived neurons are required for sex-specific learning in C. elegans

Abstract

Sex differences in behaviour extend to cognitive-like processes such as learning, but the underlying dimorphisms in neural circuit development and organization that generate these behavioural differences are largely unknown. Here we define at the single-cell level—from development, through neural circuit connectivity, to function—the neural basis of a sex-specific learning in the nematode Caenorhabditis elegans. We show that sexual conditioning, a form of associative learning, requires a pair of male-specific interneurons whose progenitors are fully differentiated glia. These neurons are generated during sexual maturation and incorporated into pre-exisiting sex-shared circuits to couple chemotactic responses to reproductive priorities. Our findings reveal a general role for glia as neural progenitors across metazoan taxa and demonstrate that the addition of sex-specific neuron types to brain circuits during sexual maturation is an important mechanism for the generation of sexually dimorphic plasticity in learning.

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Figure 1: The MCMs are newly identified male-specific neurons.
Figure 2: MCM connectivity.
Figure 3: The MCMs are required for male-specific associative learning.
Figure 4: MCM ablation does not affect other male-specific behaviours.
Figure 5: The MCMs originate from a male-specific cell division of the AMso glial cells.
Figure 6: The male AMso cells are fully differentiated glia before and after the division that generates the MCM neuron.

References

  1. Kimura, K.-I., Ote, M., Tazawa, T. & Yamamoto, D. Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain. Nature 438, 229–233 (2005)

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Ruta, V. et al. A dimorphic pheromone circuit in Drosophila from sensory input to descending output. Nature 468, 686–690 (2010)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Yang, C. F. et al. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153, 896–909 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rideout, E. J., Dornan, A. J., Neville, M. C., Eadie, S. & Goodwin, S. F. Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster. Nature Neurosci. 13, 458–466 (2010)

    Article  CAS  PubMed  Google Scholar 

  5. Stowers, L. & Logan, D. W. Sexual dimorphism in olfactory signaling. Curr. Opin. Neurobiol. 20, 770–775 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nottebohm, F. & Arnold, A. P. Sexual dimorphism in vocal control areas of the songbird brain. Science 194, 211–213 (1976)

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Keleman, K. et al. Dopamine neurons modulate pheromone responses in Drosophila courtship learning. Nature 489, 145–149 (2012)

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Sulston, J. E., Albertson, D. G. & Thomson, J. N. The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev. Biol. 78, 542–576 (1980)

    Article  CAS  PubMed  Google Scholar 

  9. Jarrell, T. A. et al. The connectome of a decision-making neural network. Science 337, 437–444 (2012)

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Sakai, N. et al. A sexually conditioned switch of chemosensory behavior in C. elegans. PLoS ONE 8, e68676 (2013)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sulston, J. E., Schierenberg, E., White, J. G. & Thomson, J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100, 64–119 (1983)

    Article  CAS  PubMed  Google Scholar 

  12. Sulston, J. E. & Horvitz, H. R. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol. 56, 110–156 (1977)

    Article  CAS  PubMed  Google Scholar 

  13. White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986)

    Article  ADS  CAS  Google Scholar 

  14. Hall, D. H. & Russell, R. L. The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions. J. Neurosci. 11, 1–22 (1991)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ward, S., Thomson, N., White, J. G. & Brenner, S. Electron microscopical reconstruction of the anterior sensory anatomy of the nematode Caenorhabditis elegans.?2UU. J. Comp. Neurol. 160, 313–337 (1975)

    Article  CAS  PubMed  Google Scholar 

  16. Varshney, L. R., Chen, B. L., Paniagua, E., Hall, D. H. & Chklovskii, D. B. Structural properties of the Caenorhabditis elegans neuronal network. PLOS Comput. Biol. 7, e1001066 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barrios, A. Exploratory decisions of the Caenorhabditis elegans male: a conflict of two drives. Semin. Cell Dev. Biol. 33, 10–17 (2014)

    Article  PubMed  Google Scholar 

  18. Ryan, D. A. et al. Sex, age, and hunger regulate behavioral prioritization through dynamic modulation of chemoreceptor expression. Curr. Biol. 24, 2509–2517 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saeki, S., Yamamoto, M. & Iino, Y. Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans. J. Exp. Biol. 204, 1757–1764 (2001)

    CAS  PubMed  Google Scholar 

  20. Vellai, T., McCulloch, D., Gems, D. & Kovács, A. L. Effects of sex and insulin/insulin-like growth factor-1 signaling on performance in an associative learning paradigm in Caenorhabditis elegans. Genetics 174, 309–316 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Srinivasan, J. et al. A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature 454, 1115–1118 (2008)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Barrios, A., Nurrish, S. & Emmons, S. W. Sensory regulation of C. elegans male mate-searching behavior. Curr. Biol. 18, 1865–1871 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Barr, M. M. & Sternberg, P. W. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature 401, 386–389 (1999)

    ADS  CAS  PubMed  Google Scholar 

  24. Barr, M. M. & García, L. R. Male mating behavior. WormBook. http://dx.doi.org/10.1895/wormbook.1.78.1 (2006)

  25. Lipton, J., Kleemann, G., Ghosh, R., Lints, R. & Emmons, S. W. Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple invertebrate. J. Neurosci. 24, 7427–7434 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Janssen, T. et al. Discovery and characterization of a conserved pigment dispersing factor-like neuropeptide pathway in Caenorhabditis elegans. J. Neurochem. 111, 228–241 (2009)

    Article  CAS  PubMed  Google Scholar 

  27. Barrios, A., Ghosh, R., Fang, C., Emmons, S. W. & Barr, M. M. PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans. Nature Neurosci. 15, 1675–1682 (2012)

    Article  CAS  PubMed  Google Scholar 

  28. Egger, B., Chell, J. M. & Brand, A. H. Insights into neural stem cell biology from flies. Phil. Trans. R. Soc. Lond. B 363, 39–56 (2008)

    Article  CAS  Google Scholar 

  29. Oikonomou, G. & Shaham, S. The glia of Caenorhabditis elegans. Glia 59, 1253–1263 (2011)

    Article  PubMed  Google Scholar 

  30. Hong, Y., Roy, R. & Ambros, V. Developmental regulation of a cyclin-dependent kinase inhibitor controls postembryonic cell cycle progression in Caenorhabditis elegans. Development 125, 3585–3597 (1998)

    CAS  PubMed  Google Scholar 

  31. Zarkower, D. Somatic sex determination. WormBook. http://dx.doi.org/10.1895/wormbook.1.84.1 (2006)

  32. Hodgkin, J. A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes Dev. 1, 731–745 (1987)

    Article  CAS  PubMed  Google Scholar 

  33. Procko, C., Lu, Y. & Shaham, S. Sensory organ remodeling in Caenorhabditis elegans requires the zinc-finger protein ZTF-16. Genetics 190, 1405–1415 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hao, L., Johnsen, R., Lauter, G., Baillie, D. & Bürglin, T. R. Comprehensive analysis of gene expression patterns of hedgehog-related genes. BMC Genomics 7, 280 (2006)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. White, J. Q. et al. The sensory circuitry for sexual attraction in C. elegans males. Curr. Biol. 17, 1847–1857 (2007)

    Article  CAS  PubMed  Google Scholar 

  36. Lee, K. & Portman, D. S. Neural sex modifies the function of a C. elegans sensory circuit. Curr. Biol. 17, 1858–1863 (2007)

    Article  CAS  PubMed  Google Scholar 

  37. Mowrey, W. R., Bennett, J. R. & Portman, D. S. Distributed effects of biological sex define sex-typical motor behavior in Caenorhabditis elegans. J. Neurosci. 34, 1579–1591 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. WormBase. AMsoR http://www.wormbase.org/species/all/anatomy_term/WBbt:0003929#01-10

  39. Jarriault, S., Schwab, Y. & Greenwald, I. A Caenorhabditis elegans model for epithelial–neuronal transdifferentiation. Proc. Natl Acad. Sci. USA 105, 3790–3795 (2008)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  40. Okada, T. S. Transdifferentiation: Flexibility in Cell Differentiation (Clarendon Press, 1991)

    Google Scholar 

  41. Eguchi, G. & Kodama, R. Transdifferentiation. Curr. Opin. Cell Biol. 5, 1023–1028 (1993)

    Article  CAS  PubMed  Google Scholar 

  42. Noctor, S. C., Martínez-Cerdeño, V., Ivic, L. & Kriegstein, A. R. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nature Neurosci. 7, 136–144 (2004)

    Article  CAS  PubMed  Google Scholar 

  43. Doetsch, F. The glial identity of neural stem cells. Nature Neurosci. 6, 1127–1134 (2003)

    Article  CAS  PubMed  Google Scholar 

  44. Ninkovic, J. & Gotz, M. Fate specification in the adult brain—lessons for eliciting neurogenesis from glial cells. Bioessays 35, 242–252 (2013)

    Article  CAS  PubMed  Google Scholar 

  45. Zuryn, S. et al. Sequential histone-modifying activities determine the robustness of transdifferentiation. Science 345, 826–829 (2014)

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Arnold, A. P. Developmental plasticity in neural circuits controlling birdsong: sexual differentiation and the neural basis of learning. J. Neurobiol. 23, 1506–1528 (1992)

    Article  CAS  PubMed  Google Scholar 

  47. WormAtlas (2002–2015) (eds Altun, Z. F. et al.) http://www.wormatlas.org/colorcode.htm

  48. Bargmann, C. I. & Avery, L. Laser killing of cells in Caenorhabditis elegans. Methods Cell Biol. 48, 225–250 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hall, D. H., Hartwieg, E. & Nguyen, K. C. Q. Modern electron microscopy methods for C. elegans. Methods Cell Biol. 107, 93–149 (2012)

    Article  CAS  PubMed  Google Scholar 

  50. Saalfeld, S., Fetter, R., Cardona, A. & Tomancak, P. Elastic volume reconstruction from series of ultra-thin microscopy sections. Nature Methods 9, 717–720 (2012)

    Article  CAS  PubMed  Google Scholar 

  51. Cardona, A. et al. TrakEM2 software for neural circuit reconstruction. PLoS ONE 7, e38011 (2012)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  52. Xu, M. et al. Computer assisted assembly of connectomes from electron micrographs: application to Caenorhabditis elegans. PLoS ONE 8, e54050 (2013)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Smoot, M. E., Ono, K., Ruscheinski, J., Wang, P.-L. & Ideker, T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27, 431–432 (2011)

    Article  CAS  PubMed  Google Scholar 

  54. Tursun, B., Patel, T., Kratsios, P. & Hobert, O. Direct conversion of C. elegans germ cells into specific neuron types. Science 331, 304–308 (2011)

    Article  ADS  CAS  PubMed  Google Scholar 

  55. Altun-Gultekin, Z. et al. A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development 128, 1951–1969 (2001)

    CAS  PubMed  Google Scholar 

  56. Barrios, A., Ghosh, R., Fang, C., Emmons, S. W. & Barr, M. M. PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans. Nature Neuroscience 15, 1675–7682 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zahn, T. R., Macmorris, M. A., Dong, W., Day, R. & Hutton, J. C. IDA-1, a Caenorhabditis elegans homolog of the diabetic autoantigens IA-2 and phogrin, is expressed in peptidergic neurons in the worm. J. Comp. Neurol. 429, 127–143 (2000)

    Article  Google Scholar 

  58. Stefanakis, N., Carrera, I. & Hobert, O. Regulatory logic of pan-neuronal gene expression in C. elegans. Neuron 87, 733–750 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mckay, S. J. et al. Gene expression profiling of cells, tissues, and developmental stages of the nematode C. elegans. Cold Spring Harb Quant. Biol. 68, 159–169 (2015)

    Article  Google Scholar 

  60. Altun, Z. F., Chen B., Wang Z. W. & Hall, D. H. High resolution map of Caenorhabditis elegans gap junction proteins. Developmental Dynamics 238, 1936–1950 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Serrano-Saiz, E. et al. Modular control of glutamatergic neuronal identity in C. elegans by distinct homeodomain proteins. Cell 155, 659–673 (2013)

    Article  CAS  PubMed  Google Scholar 

  62. Kratsios, P., Stolfi, A., Levine, M. & Hobert, O. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene. Nature Neuroscience 15, 205–214 (2011)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Bell, L. R., Stone, S., Yochem, J., Shaw, J. E. & Herman, R. K. The molecular identities of the Caenorhabditis elegans intraflagellar transport genes dyf-6, daf-10 and osm-1. Genetics 173, 1275–1286 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gerisch, B., Weitzel, C., Kober-Eisermann, C., Rottiers, V. & Antebi, A. A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev. Cell 1, 841–851 (2001)

    Article  CAS  PubMed  Google Scholar 

  65. Alkema, M. J., Hunter-Ensor, M., Ringstad, N. & Horvitz, H. R. Tyramine functions independently of octopamine in the Caenorhabditis elegans nervous system. Neuron 46, 247–260 (2005)

    Article  CAS  PubMed  Google Scholar 

  66. Kim, K. & Li, C. Expression and regulation of an FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. J. Comp. Neurol. 475, 540–550 (2004)

    Article  CAS  PubMed  Google Scholar 

  67. Beets, I. et al. Vasopressin/oxytocin-related signaling regulates gustatory associative learning in C. elegans. Science 338, 543–545 (2012)

    Article  ADS  CAS  PubMed  Google Scholar 

  68. Gruninger, T. R., Gualberto, D. G., LeBoeuf, B. & García, L. R. Integration of male mating and feeding behaviors in Caenorhabditis elegans. J. Neurosci. 26, 169–179 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yoshimura, S., Murray, J. I., Lu, Y., Waterston, R. H. & Shaham, S. mls-2 and vab-3 control glia development, hlh-17/Olig expression and glia-dependent neurite extension in C. elegans. Development 135, 2263–2275 (2008)

    Article  CAS  PubMed  Google Scholar 

  70. Haklai-Topper, L. et al. The neurexin superfamily of Caenorhabditis elegans. Gene Expr. Patterns 11, 144–150 (2011)

    Article  CAS  PubMed  Google Scholar 

  71. Gower, N. J. D. et al. Dissection of the promoter region of the inositol 1,4,5-trisphosphate receptor gene, itr-1, in C. elegans: a molecular basis for cell-specific expression of IP3R isoforms. J. Mol. Biol. 306, 145–157 (2011)

    Article  CAS  Google Scholar 

  72. Heiman, M. G. & Shaham, S. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration. Cell 137, 344–355 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to acknowledge M. Barr, in whose laboratory A.B. discovered the MCMs; WormAtlas for illustrations (reproduced with permission); T. Jarrell for contributions to the EM reconstruction; and W. Letton for the generation of strains and preliminary ablation studies. We thank M. Boxem, D. Portman, H. Baylis, L. Bianchi and R. Garcia for strains and reagents; M. Zhen, O. Hobert, I. Carrera, N. Stefanakis and S. Shaham, for unpublished reagents. Purified ascarosides were a gift from F. Schroeder to the Barr laboratory. Additional strains were obtained from the CGC, which is funded by NIH grant P40 OD010440. We thank L. Cochella, I. Carrera, S. Jarriault, and several of our close colleagues in CDB and NPP at University College London for discussions and comments on the manuscript; C. Barnes for advice on statistical analysis. This work was supported by a Master it! Scholarship Scheme (Malta and EU) to M.S., by NIH grant OD010943 to D.H.H., by Marie Curie CIG grant 618779 to R.J.P. and by a grant from The G. Harold and Leila Y. Mathers Charitable Foundation to S.W.E.; S.J.C. is supported by NIH grant 5T32GM007491; R.J.P. is a Wellcome Trust Research Career Development Fellow 095722/Z/11/Z; A.B. is supported by the Wellcome Trust Institutional Strategic Support Fund 097815/Z/11/A.

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Authors and Affiliations

Authors

Contributions

M.S., T.F., R.J.P. and A.B. conceived and performed the development and behaviour experiments. S.J.C., K.C.Q.N., S.W.E. and D.H.H. performed the ultrastructural analysis of the MCMs. S.J.C. and S.W.E. reconstructed the connectivity of the MCMs from serial EM sections. R.J.P. and A.B. co-wrote the manuscript and discussed it with all the authors.

Corresponding authors

Correspondence to Richard J. Poole or Arantza Barrios.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 The MCMs are newly identified male-specific neurons.

a, WormAtlas-style diagram depicting the morphology and position of one of the bilateral pair of MCM neurons in the head of a male worm and its projection within the nerve ring and along the ventral cord. b, Volumetric reconstruction of the MCML cell body and projection based on tracing of serial EM sections. c, Co-expression of transgenes for neuronal markers in the rab-3-positive cells identified as MCMs (indicated with dashed red circles). All photographs are lateral views of animals oriented anterior to the left and dorsal to the top except for ric-19, which are dorsal views. Transgenes are listed in Extended Data Table 1. pdf-1 (neuropeptide pigment dispersing factor); snb-1 (synaptobrevin); ida-1 (tyrosine phosphatse-like receptor, orthologue of mammalian phogrin); ric-19 (rab-2 effector); nca-1 (NALCN Na+ channel subunit); ccb-1 (voltage-gated Ca2+ channel subunit); unc-36 (voltage-gated Ca2+ channel subunit); inx-3 (gap junction innexin). D, dorsal; L, left; R, right; V, ventral. d, Diagram of the neurons that directly connect to and from the MCMs. Triangles, sensory neurons; octagons, interneurons and unidentified neurons. The thickness of the arrows is proportional to the anatomical strength of the connections (Extended Data Table 2).

Extended Data Figure 2 The MCMs are not required for other male-specific behaviours.

a, Response of intact and MCM-ablated males (inIs179(ida-1::gfp);him-8(e1489) and otIs356(rab-3::rfp)him-5(e1490)) to dilutions of ascaroside pheromones (Ascr). Graphs represent Tukey box plots of logarithmic transformations of the data; n, number of independent events (that is, entry in scoring region). t-test with Bonferroni correction was used for statistical analysis. ***P < 0.001; **P < 0.01; *P < 0.05; n.s., no statistically significant difference (P ≥ 0.05). b, Response efficiency to mate contact of intact, MCM-ablated and pdf-1(tm1996) mutant males measured as the proportion of responses out of total contacts with an hermaphrodite. Intact and MCM-ablated animals were inIs179(ida-1::gfp);him-8(e1489). Wild-type animals were him-5(e1490). A response indicates that the male placed its tail ventral down on the mate’s body and backed along it to make a turn. c, d, Proportion of good turns (c) and location of vulva efficiency (d) of intact and MCM-ablated males (inIs179(ida-1::gfp);him-8(e1489) and otIs356(rab-3::rfp)him-5(e1490)). e, Fertility (measured as proportion of cross-progeny) of intact and MCM-ablated males (otIs356(rab-3::rfp)him-5(e1490)). For be, n, number of individual animals tested. Error bars indicate s.e.m. Mann–Whitney U-test was used for statistical analysis. *P < 0.05; n.s., no statistically significant difference (P ≥ 0.05). f, Mate-searching behaviour, measured as PL values (probability of leaving food per hour) in the absence or presence of mates, of intact and MCM-ablated males (otIs356(rab-3::rfp)him-5(e1490)). n, number of individual animals tested. Two independent population assays were performed on different days. Maximum likelihood statistical analysis was used to compare PL values. Error bars indicate s.e.m. ***P <0.001; n.s., no statistically significant difference (P ≥ 0.05).

Extended Data Figure 3 The MCMs arise from a division of the AMso glial cell.

All photographs are lateral views of animals oriented anterior to the left and dorsal to the top. a, Fluorescent photographs showing the two cells expressing rnr-1::gfp co-labelled with the glial marker ptr-10::rfp and the neuronal marker rab-3::rfp in the head of males at the early and late L4 stages. The AMso and MCM cell bodies are indicated with dashed lines. b, Fluorescent images of the AMso cell body and its projection at two time points during cell division. Photos are overexposed for visualization of the projection, indicated by arrows. The chromosomes are labelled with a histone::rfp transgene, and the AMso cell body is indicated by dashed lines.

Extended Data Figure 4 AMso plasticity is regulated by AMso genetic sex.

a, Diagram of the AMso and MCM lineage. b, c, Proportion of individuals with MCMs in control animals and animals expressing sex-reversing transgenes in AMso. b, AMso masculinization with grl-2::fem-3::SL2::mCherry transgenes (oleEx18 and oleEx24). c, AMso feminization with grl-2::tra-2IC::SL2::mCherry transgenes (oleEx19 and oleEx23) and ztf-16::tra-2IC::SL2::mCherry transgene oleEx22. MCM cell fate was identified with ida-1::gfp or rab-3::yfp reporter transgenes. In the head, the grl-2 promoter drives expression in AMso and the excretory duct and pore cells, and the ztf-16 glial enhancer drives expression in the AMso and amphid sheath glia. # indicates an independent transgenic array line for each manipulation. χ2 test was used for statistical analysis; ***P < 0.001; n.s., no statistical significant difference (P ≥ 0.05); n = number of animals scored.

Extended Data Figure 5 The MCMs lose molecular and structural characteristics of glia after birth.

a, Proportion of MCMs with presence of the glial marker ptr-10::myrRfp or the neuronal marker ida-1::gfp at different stages after MCM birth. b, Electron micrograph of a cross-section of an adult male head showing the MCM and AMso cell body ultrastructure. Neighbouring tissues are colour coded following WormAtlas (http://www.wormatlas.org/colorcode.htm). Purple (pharynx), muscle (green), hypodermis (light cream), AMso (amphid socket, pink). The dendrites of the amphid neurons (amphid bundle) are not colored.

Extended Data Table 1 Reporter transgenes for neuronal markers tested for MCM expression
Extended Data Table 2 MCM connectivity
Extended Data Table 3 Cell ablations of candidate MCM progenitors
Extended Data Table 4 Mosaic analysis of sex-transformation arrays, scoring the presence of MCMs
Extended Data Table 5 Reporter transgenes for glial/AMso markers

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Sammut, M., Cook, S., Nguyen, K. et al. Glia-derived neurons are required for sex-specific learning in C. elegans. Nature 526, 385–390 (2015). https://doi.org/10.1038/nature15700

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