Robert Carrillo, PhD

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

Drosophila Late Embryonic through Late Larval Stage Body Wall Dissection: Dissection Tools and Techniques.
Drosophila Late Embryonic through Late Larval Stage Body Wall Dissection: Dissection Tools and Techniques. Cold Spring Harb Protoc. 2024 Jun 12.
PMID: 38866546

Immunohistochemistry and Morphometric Analysis of Drosophila Larval Body Wall Neuromuscular Junction Preparations.
Immunohistochemistry and Morphometric Analysis of Drosophila Larval Body Wall Neuromuscular Junction Preparations. Cold Spring Harb Protoc. 2024 Jun 12.
PMID: 38866543

Labeling of Cell Surface Proteins at the Drosophila Larval Neuromuscular Junction Using Binding Partner Peptides.
Labeling of Cell Surface Proteins at the Drosophila Larval Neuromuscular Junction Using Binding Partner Peptides. Cold Spring Harb Protoc. 2024 Jun 12.
PMID: 38866541

Using the Proximity Ligation Assay to Visualize Colocalization of Proteins at the Drosophila Larval Neuromuscular Junction.
Using the Proximity Ligation Assay to Visualize Colocalization of Proteins at the Drosophila Larval Neuromuscular Junction. Cold Spring Harb Protoc. 2024 Jun 12.
PMID: 38866544

The Drosophila Larval Neuromuscular Junction: Developmental Overview.
The Drosophila Larval Neuromuscular Junction: Developmental Overview. Cold Spring Harb Protoc. 2024 Jun 12.
PMID: 38866545

Cell Ablation Techniques for the Larval Drosophila Neuromuscular System.
Cell Ablation Techniques for the Larval Drosophila Neuromuscular System. Cold Spring Harb Protoc. 2024 Jun 12.
PMID: 38866542

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. Commun Biol. 2024 Apr 27; 7(1):507.
PMID: 38678127

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

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Ford Foundation Predoctoral Fellowship
Yale
2005 - 2008

NIH/MARC Fellowship
UCLA
1998 - 2001