Four neural structures in the Drosophila optic lobes (lamina, medulla, lobula and lobula complex) sequentially process visual information through neural networks of specialized cell types organized in a retinotopic manner. We will continue our investigations to understand how neuronal diversity is generated in the developing optic lobes, which are comprised of more than 100 cell types. Our observations suggest that neuronal specification in the medulla results from the integration of three mechanisms: (i) 800 neuroblasts express a sequence of temporal transcription factors to generate distinct types of neurons as they age, each contacting one of the 800 columns innervated by photoreceptors. (ii) The temporal series is modified locally by regional transcription factors and produces neurons that innervate multiple columns. (iii) Binary fate choice via Notch further diversifies daughters of the terminal cell division. In the posterior-most region of the developing medulla and in the progenitor region of the lobula complex, neurogenesis differs significantly with a different set of transcription factors that act not only to specify neuronal fate but also to control the precursor mode of division and the death or survival of neurons. This illustrates how complex brain structures use different strategies to adapt and produce the correct number of specific cell types with the appropriate characteristics. We will investigate the mechanisms controlling this neurogenesis.
Aim 1 : Temporal progression of neuroblasts: Timing and transition mechanisms Temporal patterning is a general mechanism to generate neural diversity in flies and vertebrates. We will explore the molecular processes controlling the temporal progression of neuroblasts in the medulla.
Aim 2. Regionalization of the medulla neuroepithelium and specialization of neuroblasts We will investigate the rules that modify the output of the temporal series in different regions of the medulla progenitor domain. This allows the local production of neurons that migrate to occupy the entire medulla.
Aim 3. Correlation between transcription factor expression and neuronal characteristics To understand how transcription networks control the characteristics of neurons, we will use large-scale single cell transcriptomics to identify regulatory interactions and determine how these define the identity of each neuron.
Aim 4. Regulation of the mode of neuroblast division and neuronal survival or death by temporal patterning We will investigate how temporal transcription factors act on the cell cycle and on pro-apoptotic genes to characterize the different strategies used by distinct parts of the optic lobes to produce specialized neurons.
Aim 5. Temporal patterning-independent neurogenesis in lobula complex progenitors We will explore the molecular mechanisms that control a different mode of neurogenesis that produces 3 types of lobula neurons without a temporal series by controlling the rapid exit of neuroblasts from proliferation. This ambitious work will allow us to identify basic principles of neural patterning and diversity generation, which have broad implications for other neuronal systems in flies and vertebrates.

Public Health Relevance

Drosophila, with its genetic amenability and small brain size, yet sophisticated behavior, has been very successfully developed as a model system to study how neural circuits form. We investigate how neuronal diversity is generated in the optic lobes that contain more than one hundred cell types and will define the molecular mechanisms that specify the different neurons that process various aspects of visual information. The principles deduced from this project will be applicable to other neural systems in more complex organisms.

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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Greenwell, Thomas
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New York University
Schools of Arts and Sciences
New York
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Konstantinides, Nikolaos; Kapuralin, Katarina; Fadil, Chaimaa et al. (2018) Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features. Cell 174:622-635.e13
Pinto-Teixeira, Filipe; Koo, Clara; Rossi, Anthony Michael et al. (2018) Development of Concurrent Retinotopic Maps in the Fly Motion Detection Circuit. Cell 173:485-498.e11
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Payre, François; Desplan, Claude (2016) RNA. Small peptides control heart activity. Science 351:226-7
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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

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