Douglas S. Portman, Ph.D.
Assistant Professor, Department of Biomedical Genetics and Department of Biology
Ph.D, 1995, University of Pennsylvania

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

The Portman laboratory studies the genetic mechanisms that generate sexual dimorphism in neural circuitry 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 these processes 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.

Our current research focuses on several areas:

• Cell fate specification and differentiation in sex-specific C. elegans neurons. The two sensory neurons and one structural cell that form each male-specific sensory ray descend postembryonically from a single multipotential precursor cell. This project aims to understand the genetic mechanisms that control male-specific neural and glial subtype specification among the progeny of this cell. Our efforts are focused on the roles of conserved bHLH and homeodomain transcription factors as well as intercellular signaling pathways.
• 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 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 similar processes in mammals.
• 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 regulate signaling through this pathway and have identified alternative signaling pathways that can compensate for the loss of polycystin function. In collaboration with K. Nehrke, Ph.D. (Dept. of Medicine), we are undertaking efforts to image calcium signaling in the polycystin neurons in vivo to better understand the their function and regulation.
• 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 DM factors simultaneously coordinate sex-specific differentiation in multiple tissue types. 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.

Portman, D.S., and Emmons, S.W. (2000)  The basic helix-loop-helix transcription factors LIN-32 and HLH-2 function together in multiple steps of a C. elegans neuronal sublineage.  Development 127:5415-5426.

Portman, D.S. and Emmons, S.W. (2004) Identification of C. elegans sensory ray genes using genome-wide expression profiling. Developmental Biology 270:499-512.

Lee, K.H. and Portman, D.S. (2007) The function of a C. elegans sensory circuit is modified by sex and developmental stage. Submitted.

Mason, D.A., Rabinowitz, J. and Portman, D.S. (2007) The DM-domain gene dmd-3 is a novel tra-1 target that coordinates multiple aspects of sexual differentiation in C. elegans. In preparation.

Miller, R.M. and Portman, D.S.  (2007) Regulation of mating behavior by a new gene family reveals distinct molecular pathways for mechanosensation in C. elegans males. In preparation.