Research Interests

Nervous system function relies on the coordinated activity of neurons of the appropriate subtype wired together to form neural circuits. Coherent behavior therefore depends critically on the developmental programs that generate neurons of the correct subtype at the correct time and place. My laboratory’s research focuses on characterizing the complex genetic networks that act during neuronal development. Understanding how these networks coordinately specify neural competence, pan-neuronal characteristics and neural-subtype identity is essential for understanding and treating neurological disease. We are also interested in understanding how neural sensory systems transduce signals that modulate behavior.
The nematode Caenorhabditis elegans provides an ideal opportunity to address these issues. C. elegans males have exactly 381 neurons; the cell lineage of each is completely known and essentially invariant. The worm is suited to sophisticated genetic analysis and its genome, the first animal genome completely sequenced, reveals a high degree of conservation among developmental mechanisms in worms, flies, mice and humans.
Our work focuses on three-celled sensory organs in the C. elegans male tail called rays. The rays are male-specific sensilla used to sense hermaphrodites during mating. Each ray contains a structural cell and two distinct sensory neurons, all three of which descend from a single precursor cell. Ray development requires the functions of two genes that encode conserved basic-helix-loop-helix (bHLH) transcription factors: lin-32, the C. elegans atonal/MATH ortholog, and hlh-2, the E/daughterless ortholog. lin-32-family genes are important in many animals including flies and mice for the specification of neuronal fates, particularly in sensory systems. We have previously shown that mutations in these factors disrupt the ray developmental lineage at multiple points, suggesting that LIN-32 and HLH-2 activate multiple targets important for different steps of ray cell fate specification. To find additional components of the ray developmental pathway, we have used DNA microarrays to compare gene expression between males with extra rays and males lacking rays. Using this approach, we have identified a number of new ray differentiation genes (downstream targets of the ray developmental pathway) as well as regulatory factors that could be components of these pathways. We are focusing our efforts on understanding the functions of several of these genes in ray function. One, the beta-tubulin isotype tbb-4, is expressed in all ray neurons and may have roles in generating the specific ciliated structure the is essential to the sensory function of these cells. In addition, our microarray studies have identified four novel genes (cwp-1 through -4) that encode secreted proteins expressed in ray neurons that may function with the TRPP channel formed by the polycystins LOV-1 and PKD-2 to sense mechanosensory signals during male mating behavior.
We are currently taking a multidisciplinary approach (using forward and reverse genetics, biochemistry, genomics and bioinformatics) to identify and characterize components of the ray developmental pathway and understand how their functions are integrated as part of a complex genetic network. We expect that these relationships will lend insight into similar, less experimentally-accessible processes in higher organisms.

1. 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 24:5415-26.

2. Portman, D.S. and Emmons, S.W. (2003) Expression profiling identifies sensory ray genes in C. elegans. Submitted.