Visual information is processed through specialized channels: In each ommatidium of the Drosophila retina, motion is processed by the six ?outer photoreceptors? that project to the lamina. Color is detected by photoreceptors R7 and R8 that belong to two subtypes: In the p subtype, pR7 expresses UV-sensitive Rh3 and pR8 contains Blue-Rh5. In the y subtype, UV-Rh4 in yR7 is coupled to Green-Rh6 in yR8. We offer to study the signal that relays this information from R7 to R8 to coordinate the expression of Rhodopsins (Aim 1). We will extend this work to the signals originating from outer photoreceptors, which control the division of lamina precursor cells (LPCs) by releasing Hedgehog, and which induce the differentiation of the lamina neurons L1-L5 by releasing EGF/Spitz from their termini.
In Aim 2, we will determine how the development of photoreceptors and of their lamina targets is coordinated. We also discovered that distinct glial cell types play specific roles in patterning each of the five lamina cell types. This has prompted us to study how glia originate in different regions of the optic lobes, how they migrate to take on their final positions, and how they mediate differentiation signals to L1-L5 (Aim 3).
Aim 1. Specification of the R8 subtype fate by signaling from R7 photoreceptors. We will analyze the significance of multiple BMP/Activin ligands that participate in R7-R8 communication, and test whether they signal through their canonical receptors. The signal is reinforced in R8 by a bistable loop involving the Warts tumor suppressor and a growth regulator, Melted. We will determine whether Mad/Smad2 activate melted or repress warts, to generate and maintain the correct ommatidial R7 and R8 subtypes. The BMP/Activin signals are restricted to a single ommatidium, and do not diffuse to neighboring ommatidia. We have shown that the Hibris cell adhesion molecule limits this diffusion and will study how it affects R7-R8 pairing. Expanded signal diffusion leads to clusters of Rh5 R8s that are reminiscent of clusters of pigmentation in the eye of Eristalinus flies. We will use our evo-devo expertise to study how the signal may be propagated in specific species.
Aim 2 : How do signals from photoreceptors specify the five cell types of the lamina? We will explore how signals from the outer photoreceptors regulate proliferation and cell cycle exit to generate lamina precursors. We will then manipulate EGFR to ask how Spitz levels from photoreceptors affect lamina differentiation. We will also test how EGFR/Notch antagonism among lamina precursors contributes to L1-L5 diversification.
Aim 3. The role of different glial populations for the specification of lamina neurons. We have evidence that the order and kinetics of lamina cell determination is coupled with glial development. We will manipulate glial cells to determine how they are involved in mediating the EGF signal from photoreceptors. Using genomics and live imaging, we will characterize the different populations of glia and determine their origin. We will then develop a quantitative and predictive model of the interactions that contribute to specifying lamina neuronal diversity.

Public Health Relevance

Drosophila, with its genetic amenability and simple retina, yet very sophisticated visual performances, has been very successfully developed as a model system to study how sensory systems are built during development. We investigate how photoreceptors coordinate the expression of their Rhodopsins that detect various wavelengths of light, and how they communicate with their targets in the optic lobes to build retinotopy and neuronal diversity. The principles deduced from this project will be applicable to other sensory systems such as the mammalian retina.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Neurogenesis and Cell Fate Study Section (NCF)
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Neuhold, Lisa
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New York University
Schools of Arts and Sciences
New York
United States
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Minkina, Olga; Desplan, Claude (2018) Large-Scale CRISPR-Mediated Somatic Mutagenesis Identifies a Signaling Pathway that Guides Retinal Development. Neuron 98:1-3
Holguera, Isabel; Desplan, Claude (2018) Neuronal specification in space and time. Science 362:176-180
Rossi, Anthony M; Desplan, Claude (2017) Asymmetric Notch Amplification to Secure Stem Cell Identity. Dev Cell 40:513-514
Wells, Brent S; Pistillo, Daniela; Barnhart, Erin et al. (2017) Parallel Activin and BMP signaling coordinates R7/R8 photoreceptor subtype pairing in the stochastic Drosophila retina. Elife 6:
Fernandes, Vilaiwan M; Chen, Zhenqing; Rossi, Anthony M et al. (2017) Glia relay differentiation cues to coordinate neuronal development in Drosophila. Science 357:886-891
Perry, Michael; Konstantinides, Nikos; Pinto-Teixeira, Filipe et al. (2017) Generation and Evolution of Neural Cell Types and Circuits: Insights from the Drosophila Visual System. Annu Rev Genet 51:501-527
Rossi, Anthony M; Fernandes, Vilaiwan M; Desplan, Claude (2017) Timing temporal transitions during brain development. Curr Opin Neurobiol 42:84-92
Chen, Zhenqing; Del Valle Rodriguez, Alberto; Li, Xin et al. (2016) A Unique Class of Neural Progenitors in the Drosophila Optic Lobe Generates Both Migrating Neurons and Glia. Cell Rep 15:774-786
Pinto-Teixeira, Filipe; Konstantinides, Nikolaos; Desplan, Claude (2016) Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system. FEBS Lett 590:2435-2453
Courgeon, Maximilien; Konstantinides, Nikolaos; Desplan, Claude (2015) Cell competition: dying for communal interest. Curr Biol 25:R339-41

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