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Cell Surface Protein Interactions Controlling Photoreceptor Synaptic Targeting and Amacrine Cell Fate in the Drosophila Visual System

Award Number: R01EY028116
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Many cell surface proteins (CSPs) essential for neural development have been identified, but we still lack an overall understanding of how cell-cell interactions mediated by these CSPs program assembly of complex neural circuits. Our long-term goal is to understand these processes. Many years ago, it was proposed that, in “hard-wired” neural structures such as the fish retinotectal system and the insect optic lobe, each individual neuron is labeled by “identification tags” that control synaptic specificity, and that these tags are represented by specific CSPs called “surface labels”. The hypotheses predicted that surface labels that control synaptic specificity should be: 1) expressed on small subsets of neurons in each brain area, 2) recognized by receptors whose expression is also restricted to neuronal subsets, 3) required for formation of specific synaptic connections, 4) encoded by families of related genes. We discovered a network of interacting CSPs that satisfies all of these criteria, using an in vitro interaction screen of Drosophila CSPs. In this screen, we identified a subfamily of 21 2-Ig domain proteins, the Dprs, that selectively bind to another subfamily of 9 3-Ig domain proteins, the DIPs, forming a network called the Dpr-ome. In the visual system, neurons expressing a particular Dpr tend to be presynaptic to neurons expressing a DIP to which that Dpr binds in vitro. The objectives of the present application are to understand how Dpr-DIP interactions regulate competition among visual system neurons for neurotrophic signals, and to determine whether and how binding of a presynaptic Dpr to its postsynaptic DIP partner controls formation and function of synapses. The primary hypothesis underlying this application is that engagement of Dprs with their DIP partners provides information that influences cell fates and patterns of synaptic connections in the optic lobe. In particular, we hypothesize that trans-synaptic interactions between Dpr11 and its partner DIP-¿ are required for determination of cell numbers and specification of connections in the color vision circuit. Dpr11 is expressed by a subtype of UV photoreceptors, the yellow (y) R7s. The primary synaptic target for R7s is the amacrine neuron Dm8. DIP-¿ is expressed by a subset of Dm8s (“yDm8s”) that selectively arborizes with yR7s. yDm8s that do not successfully innervate R7s die. DIP-¿ controls their ability to compete for Dpr11-expressing yR7 targets and thereby regulates cell death. We plan to attain our objectives through two specific aims. Aim 1: Control of competitive interactions among Dm8s by Dpr11 and DIP-¿. Aim 2: Control of synaptic selection by Dpr11-DIP-¿ interactions. The expected outcome of the proposed research will be the acquisition of new insights into the mechanisms by which interactions among CSPs control the assembly of neural circuits in the developing visual system. This will have a significant positive impact for human health by increasing our understanding of conserved mechanisms involved in development and disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Vision Research	000	5	2/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $324,950 )
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Vision Research	000	5	5/27/2022	NON-COMPETING CONTINUATION	$324,950
														Subtotal = $324,950

Issue Date FY: 2021 ( Subtotal = $324,950 )
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Vision Research	000	4	5/14/2021	NON-COMPETING CONTINUATION	$324,950
														Subtotal = $324,950

Issue Date FY: 2020 ( Subtotal = $335,000 )
2020	2020	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Vision Research	000	3	6/1/2020	NON-COMPETING CONTINUATION	$335,000
														Subtotal = $335,000

Issue Date FY: 2019 ( Subtotal = $335,000 )
2019	2019	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Vision Research	000	2	5/24/2019	NON-COMPETING CONTINUATION	$335,000
														Subtotal = $335,000

Issue Date FY: 2018 ( Subtotal = $335,000 )
2018	2018	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Vision Research	000	1	7/30/2018	NEW	$335,000
														Subtotal = $335,000

Grand Total All Awards = $1,654,900

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Cell Surface Protein Interactions Controlling Photoreceptor Synaptic Targeting and Amacrine Cell Fate in the Drosophila Visual System

Award Number: R01EY028116

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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