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
University of California, Los Angeles
BS - Cybernetics
Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila.
Cheng S, Ashley J, Kurleto JD, Lobb-Rabe M, Park YJ, Carrillo RA, Özkan E. Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila. Elife. 2019 01 28; 8.
Control of Synaptic Connectivity by a Network of Drosophila IgSF Cell Surface Proteins.
Carrillo RA, Özkan E, Menon KP, Nagarkar-Jaiswal S, Lee PT, Jeon M, Birnbaum ME, Bellen HJ, Garcia KC, Zinn K. Control of Synaptic Connectivity by a Network of Drosophila IgSF Cell Surface Proteins. Cell. 2015 Dec 17; 163(7):1770-1782.
The translational regulator Cup controls NMJ presynaptic terminal morphology.
Menon KP, Carrillo RA, Zinn K. The translational regulator Cup controls NMJ presynaptic terminal morphology. Mol Cell Neurosci. 2015 Jul; 67:126-36.
An extracellular interactome of immunoglobulin and LRR proteins reveals receptor-ligand networks.
Özkan E, Carrillo RA, Eastman CL, Weiszmann R, Waghray D, Johnson KG, Zinn K, Celniker SE, Garcia KC. An extracellular interactome of immunoglobulin and LRR proteins reveals receptor-ligand networks. Cell. 2013 Jul 03; 154(1):228-39.
Is instability good for the brain?
Carrillo RA, Menon K, Zinn K. Is instability good for the brain? Neuron. 2013 Feb 20; 77(4):599-601.
Development and plasticity of the Drosophila larval neuromuscular junction.
Menon KP, Carrillo RA, Zinn K. Development and plasticity of the Drosophila larval neuromuscular junction. Wiley Interdiscip Rev Dev Biol. 2013 Sep-Oct; 2(5):647-70.
Presynaptic activity and CaMKII modulate retrograde semaphorin signaling and synaptic refinement.
Carrillo RA, Olsen DP, Yoon KS, Keshishian H. Presynaptic activity and CaMKII modulate retrograde semaphorin signaling and synaptic refinement. Neuron. 2010 Oct 06; 68(1):32-44.
Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit.
Mosca TJ, Carrillo RA, White BH, Keshishian H. Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit. Proc Natl Acad Sci U S A. 2005 Mar 01; 102(9):3477-82.
Uridine insertion/deletion RNA editing in Leishmania tarentolae mitochondria shows cell cycle dependence.
Carrillo R, Thiemann OH, Alfonzo JD, Simpson L. Uridine insertion/deletion RNA editing in Leishmania tarentolae mitochondria shows cell cycle dependence. Mol Biochem Parasitol. 2001 Mar; 113(1):175-81.
Ford Foundation Predoctoral Fellowship
2005 - 2008
1998 - 2001