Synaptic connectivity constitutes an integral part of neuronal identity. The recent reconstruction of the connectome of the C.elegans male and its comparison to the long known connectome of the hermaphrodite (a derived female) reveal a sexually dimorphic dimension of neuronal identity: Some defined neuron types that are present in both hermaphrodites and males show sexually dimorphic synaptic connectivity patterns. We propose to dissect the regulatory programs that specify sexual dimorphic identity, as manifested by dimorphic synaptic connectivity features. Specifically, we propose here to (1) reliably and easily visualize sexually dimorphic synaptic connectivity patterns in transgenic animals using GFP-based reporter systems; (2) study aspects of the establishment, maintenance and autonomy of these dimorphic synapses and (3) identify molecules through a candidate gene approach and unbiased profiling approach that genetically program these dimorphic patterns of connectivity and identity. We expect that our studies will provide novel insights into the currentl little explored sexual dimension of neuronal identity.

Public Health Relevance

There are anatomical differences in the brains of males and females in many different species. These anatomical differences are only poorly characterized. Moreover, while some global signals that induce sex differences are well appreciated, the nature of the regulatory programs that instruct dimorphisms in brain anatomy and function are poorly defined. In the roundworm C. elegans anatomical brain differences between its two different sexes have been described in exquisite detail. We propose here to exploit the genetic amenability of C. elegans to analyze how anatomical brain dimorphisms develop and propose to identify genes that are involved in specifying these differences.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Leenders, Miriam
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Graduate Schools
New York
United States
Zip Code
Hart, Michael P; Hobert, Oliver (2018) Neurexin controls plasticity of a mature, sexually dimorphic neuron. Nature 553:165-170
Bayer, Emily A; Hobert, Oliver (2018) Past experience shapes sexually dimorphic neuronal wiring through monoaminergic signalling. Nature 561:117-121
Vidal, Berta; Aghayeva, Ulkar; Sun, Haosheng et al. (2018) An atlas of Caenorhabditis elegans chemoreceptor expression. PLoS Biol 16:e2004218
Weinberg, Peter; Berkseth, Matthew; Zarkower, David et al. (2018) Sexually Dimorphic unc-6/Netrin Expression Controls Sex-Specific Maintenance of Synaptic Connectivity. Curr Biol 28:623-629.e3
Serrano-Saiz, Esther; Pereira, Laura; Gendrel, Marie et al. (2017) A Neurotransmitter Atlas of the Caenorhabditis elegans Male Nervous System Reveals Sexually Dimorphic Neurotransmitter Usage. Genetics 206:1251-1269
Kratsios, Paschalis; Kerk, Sze Yen; Catela, Catarina et al. (2017) An intersectional gene regulatory strategy defines subclass diversity of C. elegans motor neurons. Elife 6:
Oren-Suissa, Meital; Bayer, Emily A; Hobert, Oliver (2016) Sex-specific pruning of neuronal synapses in Caenorhabditis elegans. Nature 533:206-11
Pereira, Laura; Kratsios, Paschalis; Serrano-Saiz, Esther et al. (2015) A cellular and regulatory map of the cholinergic nervous system of C. elegans. Elife 4:
Arlotta, Paola; Hobert, Oliver (2015) Homeotic Transformations of Neuronal Cell Identities. Trends Neurosci 38:751-762
Deneris, Evan S; Hobert, Oliver (2014) Maintenance of postmitotic neuronal cell identity. Nat Neurosci 17:899-907