Description of Research Expertise
Research Interests
- Molecular mechanisms of axon growth and guidance during nervous system development.
- How axon guidance receptors specify attractive and repulsive signals and transmit these signals to the navigating growth cone.
- Non-canonical roles for guidance receptors as transcriptional regulators.
- Formation of Neural Circuits at the Midline
- Transcriptional Regulation of Neuronal Morphogenesis
- Generation of Neuronal Diversity

Key words: Axon guidance, developmental neuroscience, circuit assembly, Slit, Robo, Netrin, DCC, receptor signaling.

Description of Research
How axons in the developing nervous system successfully navigate to their correct targets is a fundamental problem in neurobiology. Understanding the mechanisms that mediate axon guidance will give important insight into how the nervous system is correctly wired during development and may have implications for therapeutic approaches to developmental brain disorders and nerve regeneration. Achieving this understanding will require unraveling the molecular logic that ensures the proper expression and localization of axon guidance cues and receptors, and elucidating the signaling events that regulate the growth cone cytoskeleton in response to guidance receptor activation.

The Slit ligand and Roundabout (Robo) receptors, and the Netrin ligand and DCC/UNC5 receptors are two important evolutionary conserved ligand/receptor systems that contribute to proper connectivity in both the vertebrate and invertebrate nervous systems. These molecules are also known to influence neuronal and mesodermal cell migration, suggesting that determining their function may have broad implications for understanding diseases of nervous system development, many of which have their root in defective cell migration and/or axon guidance. The research in my laboratory addresses the dynamics of axon guidance receptor expression and signaling, and exploits the powerful genetic and molecular approaches available in Drosophila.

We have also discovered that in addition to its canonical role in signaling locally to regulate growth cone movement and morphology, the Frazzled/DCC receptor can also act as a transcription factor to regulate gene expression. In this context, the receptor is cleaved to generate a soluble intracellular domain that can translocate to the nucleus where it activates transcription of key target genes.