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Research Overview

Genetic control of sex differences in development and behavior in C. elegans

The Portman laboratory studies the genetic mechanisms that generate sexual dimorphism in development and behavior. Our efforts focus on the powerful nematode model system Caenorhabditis elegans, because of its exceptional tractability and conserved battery of genetic mechanisms. By its nature, our work is fundamentally interdisciplinary, drawing from molecular genetics, developmental biology, molecular/cellular neuroscience, and animal behavior. Understanding sex differences in development and behavior is not only of biological interest; we hope to also understand the genetic basis for the significant sex differences in the incidence of neurological and mental health disorders such as mental retardation and autism.

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Our current research focuses on several areas:

• Cell fate specification and differentiation in sex-specific C. elegans neurons. The rays are sensory specializations present in the adult C. elegans male tail; they are used by the male to sense the hermaphrodite during mating behavior. The two sensory neurons and one structural cell that comprise each ray descend postembryonically from a single multipotential precursor cell, providing an excellent model for understanding how specific neural cell types are generated from progenitor cells. The bHLH factor LIN-32 (the worm MATH/atonal ortholog) has multiple regulatory roles in ray development. Recently we have found that lin-32 acts not only to specify the ray precursor cell but also to pattern the neural subtype of its progeny. Our current efforts are focused on the roles of Wnt signaling and other transcription factors in specifying male-specific differentiated cell fates.
• Sex-specificity in neural circuit function and behavior. We have recently identified novel and intriguing sex differences in olfaction and locomotion, two behaviors mediated by (nominally) non-sex-specific circuitry in C. elegans. We have found that at least some of these differences are regulated by a conserved family of poorly-understood sex-determination genes, the DM factors. We are currently working to understand how sex determination modifies the development and/or function of the olfactory and locomotory circuits, with the hope of illuminating pathways that will be important for creating sex differences in neural function in mammals.
• Sex-specificity in morphogenesis. We have also found that DM domain genes orchestrate a complex set of sex-specific morphogenetic events in the C. elegans tail. We are working to understand how two of these factors, dmd-3 and mab-3, simultaneously coordinate sex-specific differentiation of several cell types in the male tail. Given that DM domain genes have been implicated in human sex-reversal syndromes, this work will shed important light on regulatory mechanisms that may underlie a variety of birth defects.
• Sensory transduction in male mating behavior. Sensory signaling in the ray neurons is mediated by the polycystins, transmembrane proteins that are thought to be mechanosensors. Disruption of human homologs of these genes leads to Autosomal Dominant Polycystic Kidney Disease, a significant cause of morbidity and mortality in the US. We have recently found that five novel, male-specific C. elegans genes (the cwp genes) may regulate signaling through this pathway and have identified alternative signaling pathways that can compensate for the loss of polycystin function.

Research Interests

• Genetics of development and behavior in C. elegans
• Neural cell fate specification
• Sex differences in neural circuit function
• Sexual dimorphism in developmental patterning