This proposal is a renewal of 5R01EY017916-04 "Mapping the optic lobes for color vision". Visual information gathered by the Drosophila eye is first processed in the optic lobes, lamina, medulla and lobula complex. The medulla is the first relay in the neural network for color vision, but it is the second step in the motion detection pathway. In the previous granting period, we have defined over 70 cell types that form overlapping retinotopic maps before projecting to the lobula complex. Because the medulla contains a finite number of neurons and connections that can be studied in exquisite detail, we can address fundamental questions about the development and function of a sophisticated neural structure. We present experiments to understand how optic neuron diversity is generated and how these neurons establish their retinotopic connections to photoreceptors. This will produce knowledge and tools that we will then use to analyze the function of individual neurons in optic pathways through electrophysiology and behavior assays.
Three specific aims will help us reach these goals. (1). Sequential neuroblast (NB) switching generates neuronal diversity. We have discovered that the NBs generated as a wave of differentiation from the medulla neuroepithelium express sequentially at least three transcription factors in a process similar to the sequence observed in embryonic NBs. The neurons emerging from these NBs maintain expression of these genes and become different cell types. We will identify new NB and neuronal markers and identify the adult neuronal cell types derived from larval neurons marked by combinations of TFs. (2). Regionalization of medulla neuroepithelium and specialization of neuroblasts. The types of neurons generated by the sequentially generated NBs differ in distinct regions of the crescent shaped medulla Outer Proliferation Center (OPC). In the central part, young NBs produce both local columnar cells that remain where they were generated, as well as a smaller number of non-columnar neurons that migrate to occupy their retinotopic position in the entire adult medulla. We will analyze how the lineage of NBs is modified by their position along the OPC. We will then manipulate the positional identity of NBs and analyze the consequence on the neuronal composition of the medulla. We will thus define the combinatorial transcription factor code specifying medulla neuron types and will relate it to their adult fates. (3). Function of individual medulla neurons. We will record electrophysiological activity of these neurons in response to various light stimuli. We will continue our analysis of neurons involved in motion detection and extend this analysis of medulla neurons involved in chromatic pathways. The tools generated in aims 1 and 2 will allow us to silence of stimulate these neurons through 'intersectional'expression to analyze the motion and color behavior of flies using our flight simulator.

Public Health Relevance

Drosophila, with its genetic amenability and the small size of its brain, yet its sophisticated behavior, has been very successfully developed as a model system to study how neural circuits control behavior. We investigate how the medulla part of the optic lobes develop and function by defining the molecular code that specifies medulla neurons and use electrophysiology and a flight simulator to understand their function in motion detection and color discrimination. The principles deduced from this project will be applicable to other sensory systems in more complex organisms.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017916-07
Application #
8411124
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Steinmetz, Michael A
Project Start
2007-02-01
Project End
2016-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
7
Fiscal Year
2013
Total Cost
$325,759
Indirect Cost
$112,009
Name
New York University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Neriec, Nathalie; Desplan, Claude (2014) Different ways to make neurons: parallel evolution in the SoxB family. Genome Biol 15:116
Bertet, Claire; Li, Xin; Erclik, Ted et al. (2014) Temporal patterning of neuroblasts controls Notch-mediated cell survival through regulation of Hid or Reaper. Cell 158:1173-86
Behnia, Rudy; Clark, Damon A; Carter, Adam G et al. (2014) Processing properties of ON and OFF pathways for Drosophila motion detection. Nature 512:427-30
Morante, Javier; Vallejo, Diana M; Desplan, Claude et al. (2013) Conserved miR-8/miR-200 defines a glial niche that controls neuroepithelial expansion and neuroblast transition. Dev Cell 27:174-87
Li, Xin; Erclik, Ted; Bertet, Claire et al. (2013) Temporal patterning of Drosophila medulla neuroblasts controls neural fates. Nature 498:456-62
Morante, Javier; Erclik, Ted; Desplan, Claude (2011) Cell migration in Drosophila optic lobe neurons is controlled by eyeless/Pax6. Development 138:687-93
Vogt, Nina; Desplan, Claude (2010) Developmental biology. Flipping the light switch. Science 330:454-5
Buckingham, Margaret; Desplan, Claude (2010) Developmental mechanisms, patterning and evolution. Curr Opin Genet Dev 20:343-5
Yamaguchi, Satoko; Desplan, Claude; Heisenberg, Martin (2010) Contribution of photoreceptor subtypes to spectral wavelength preference in Drosophila. Proc Natl Acad Sci U S A 107:5634-9
Griffin, Ruth; Sustar, Anne; Bonvin, Marianne et al. (2009) The twin spot generator for differential Drosophila lineage analysis. Nat Methods 6:600-2

Showing the most recent 10 out of 14 publications