The morphological diversity among neurons is enormous and critical to their function, yet many gaps in our knowledge remain concerning how this diversity is genetically encoded. As with vertebrate motor neurons, the motor neurons of Drosophila melanogaster establish highly specific synapses on the correct muscle fibers in the appendages and also elaborate highly stereotyped dendritic arbors in the central nervous system (CNS). In the previous funding period, we characterized the individual progeny and transcription factor codes that govern neuronal identities for one of the largest neuroblast lineages that give rise to motor neurons and neuropil glia. We further described the role of Ig domain family members in establishing certain aspects of motor neuron identities. Live imaging provided unprecedented access to the relevant stages of motor neuron maturation during pupal stages. In the coming funding period we will extend these findings to understand how transcription factors in post- mitotic neurons regulate their target genes. We will carry out a series of whole genome and single cell studies to obtain this information on a genome-wide scale. Finally, we will analyze additional members of the Ig domain superfamily to assess what other roles, besides axon targeting, they play in motor neuron morphology during development.

Public Health Relevance

Genetic and molecular approaches in the fruit fly, Drosophila melanogaster, will be used to dissect the complex problem of how neurons obtain their unique identities. By focusing on a set of motor neurons used for walking in the adult fly, the goal is to gain insights into how neurons achieve their exquisite synaptic specificities and dendritic architectures, and how perturbations to these morphologies affects coordinated leg movements, such as walking by adult flies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS070644-11
Application #
9971790
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Lavaute, Timothy M
Project Start
2010-04-01
Project End
2025-02-28
Budget Start
2020-06-01
Budget End
2021-02-28
Support Year
11
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biochemistry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Enriquez, Jonathan; Rio, Laura Quintana; Blazeski, Richard et al. (2018) Differing Strategies Despite Shared Lineages of Motor Neurons and Glia to Achieve Robust Development of an Adult Neuropil in Drosophila. Neuron 97:538-554.e5
Mann, Richard S; Howard, Clare E (2016) The Importance of Timing. Cell 164:347-8
Bouchard, Matthew B; Voleti, Venkatakaushik; Mendes, César S et al. (2015) Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms. Nat Photonics 9:113-119
Enriquez, Jonathan; Venkatasubramanian, Lalanti; Baek, Myungin et al. (2015) Specification of individual adult motor neuron morphologies by combinatorial transcription factor codes. Neuron 86:955-970
Mendes, César S; Bartos, Imre; Márka, Zsuzsanna et al. (2015) Quantification of gait parameters in freely walking rodents. BMC Biol 13:50
Mann, Richard S (2014) Neuroscience. The Michael Jackson fly. Science 344:48-9
Mendes, César S; Rajendren, Soumya V; Bartos, Imre et al. (2014) Kinematic responses to changes in walking orientation and gravitational load in Drosophila melanogaster. PLoS One 9:e109204
Zhang, Feifan; Bhattacharya, Abhishek; Nelson, Jessica C et al. (2014) The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types. Development 141:422-35
Baek, Myungin; Enriquez, Jonathan; Mann, Richard S (2013) Dual role for Hox genes and Hox co-factors in conferring leg motoneuron survival and identity in Drosophila. Development 140:2027-38
Doitsidou, Maria; Flames, Nuria; Topalidou, Irini et al. (2013) A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans. Genes Dev 27:1391-405

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