The long term goals of my lab are to understand the molecules and developmental programs that regulate neuronal development and 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 21-member Dprs and the 9-member 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 (35) and muscle targets (30) in each hemisegment. Motor neurons in the ventral nerve cord must send their axons into the periphery and innervate their appropriate muscle target(s) in a highly stereotypic pattern. This system provides an ideal platform in which to tease apart the molecular determinants that contribute to this hard-wired specificity. We recently 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.
Visual system: The fly visual circuit is composed of the retina, lamina, medulla, lobula, and lobula plate. Photoreceptors in the retina receive light stimuli and relay signals to downstream neurons which integrate that information to elicit an appropriate behavioral response. The laminar organization of synaptic connections, complete EM reconstruction of the fly brain, and a myriad of genetic tools provide an excellent system to interrogate the mechanisms underlying neural wiring. Dprs and DIPs are expressed in subsets of neurons in the visual circuit and synaptic partners express corresponding Dpr-DIP interacting pairs. Utilizing genetic and functional tools, we are investigating if Dpr-DIP combinations provide a cell-surface signature to specify synaptic partner matching.
Yale School of Medicine
New Haven, CT
PhD - Pharmacology
2009
University of California, Los Angeles
Los Angeles
BS - Cybernetics
2001
Neuronal Wiring Receptors Dprs and DIPs Are GPI Anchored and This Modification Contributes to Their Cell Surface Organization.
Neuronal Wiring Receptors Dprs and DIPs Are GPI Anchored and This Modification Contributes to Their Cell Surface Organization. eNeuro. 2024 Feb; 11(2).
PMID: 38233143
hkb is required for DIP-a expression and target recognition in the Drosophila neuromuscular circuit.
hkb is required for DIP-a expression and target recognition in the Drosophila neuromuscular circuit. bioRxiv. 2023 Oct 17.
PMID: 37905128
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila.
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila. Nat Commun. 2023 07 24; 14(1):4452.
PMID: 37488133
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death.
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death. bioRxiv. 2023 Apr 10.
PMID: 37090512
Dpr10 and Nocte are required for Drosophila motor axon pathfinding.
Dpr10 and Nocte are required for Drosophila motor axon pathfinding. Neural Dev. 2022 10 21; 17(1):10.
PMID: 36271407
Systematic expression profiling of Dpr and DIP genes reveals cell surface codes in Drosophila larval motor and sensory neurons.
Systematic expression profiling of Dpr and DIP genes reveals cell surface codes in Drosophila larval motor and sensory neurons. Development. 2022 05 15; 149(10).
PMID: 35502740
Structural and Functional Synaptic Plasticity Induced by Convergent Synapse Loss in the Drosophila Neuromuscular Circuit.
Structural and Functional Synaptic Plasticity Induced by Convergent Synapse Loss in the Drosophila Neuromuscular Circuit. J Neurosci. 2021 02 17; 41(7):1401-1417.
PMID: 33402422
Temporal transcription factors determine circuit membership by permanently altering motor neuron-to-muscle synaptic partnerships.
Temporal transcription factors determine circuit membership by permanently altering motor neuron-to-muscle synaptic partnerships. Elife. 2020 05 11; 9.
PMID: 32391795
Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila.
Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila. Dev Neurobiol. 2019 04; 79(4):335-349.
PMID: 31002474
Transsynaptic interactions between IgSF proteins DIP-a and Dpr10 are required for motor neuron targeting specificity.
Transsynaptic interactions between IgSF proteins DIP-a and Dpr10 are required for motor neuron targeting specificity. Elife. 2019 02 04; 8.
PMID: 30714906
Ford Foundation Predoctoral Fellowship
Yale
2005 - 2008
NIH/MARC Fellowship
UCLA
1998 - 2001