B.S., Cybernetics, University of California, Los Angeles, 2001
Ph.D., Pharmacology, Yale School of Medicine, 2009
HOW IS NEURAL CIRCUIT SPECIFICITY ACHIEVED?! The long term goals of my lab are to understand the molecules and developmental programs that regulate neuronal wiring. To this end, we investigated the novel interactions between two subfamilies of the immunoglobulin superfamily in Drosophila melanogaster (in collaboration with Christopher Garcia at Stanford and Engin Ozkan at the University of Chicago; Ozkan et al., 2013): the defective proboscis extension response proteins (Dprs; Nakamura el al., 2002), encompassing 21 members, and the 9-member Dpr-interacting proteins (DIPs). Previously, we found that an interacting Dpr-DIP pair functions at various developmental stages including motor neuron development at the larval neuromuscular junction (NMJ) and wiring and cell survival in the pupal optic lobe (Carrillo et al., 2015). In my lab, we will explore the functions of cell surface proteins, including Dprs and DIPs, and their downstream signaling cascades in nervous system development. Understanding these mechanisms will also contribute to our understanding of neurological diseases marked by alternations in connectivity such as autism spectrum disorder.
Neuromuscular system: The larval neuromuscular circuit is highly stereotyped with single cell resolution due to the limited number of motor neurons (32) and muscle targets (30) per hemisegment. Motor neurons in the ventral nerve cord must send their axons into the periphery and faithfully innervate their appropriate muscle target(s). This system provides an ideal platform in which to tease apart the molecular determinants that contribute to this hard-wired specificity. We found that a Dpr-DIP pair controls the targeting of a specific motor neuron to its corresponding muscle. This unique phenotype will serve as a model to delve deeper into the molecules and mechanisms that function in Dpr-DIP regulated wiring using a combination of forward and reverse genetics, biochemistry, electrophysiology, behavioral assays, and cell culture studies.
Ventral nerve cord: Upstream of muscle innervation, motor neurons receive input from interneurons in the ventral nerve cord (VNC; analogous to the vertebrate spinal cord). These interneurons integrate information from the central brain as well as sensory input in order to produce an appropriate motor response. Here we ask: does interneuron-motor neuron connectivity use similar mechanisms to those used in the neuromuscular system? Unlike the NMJ, these neuronal processes are not sparse enough to allow for single-cell resolution. However, we will utilize genetic tools that allow for single cell resolution of dendritic arbors and axon terminals when combined with confocal microscopy. Simultaneous optogenetic manipulation and calcium imagining, in addition to electrophysiology, will allow us to monitor perturbations in circuit function.