Animal locomotion requires the coordinated firing of motor neurons that trigger the contraction of muscles in the appendages, such as the legs. In addition, coordination requires feedback from sensory neurons located in the appendages. To understand how functional motor neuron circuits form, this project will investigate the development and function of the motor circuit used by the adult fruit fly for walking. The combinatorial transcription factor code required to give each motor neuron its particular identity will be deciphered using both novel genetic and molecular biology approaches. Once identified, the consequences on walking of perturbing small numbers of motor neurons will be analyzed. Finally, the role of sensory feedback from mechanosensory organs in the legs will be characterized. Together, these studies will lay the ground work for a new model genetic system for studying motor circuits in a genetically tractable animal that, unlike its larval counterpart, uses appendages for locomotion.

Public Health Relevance

Animal locomotion requires the coordinated firing of motor neurons that trigger the contraction of muscles in the appendages, such as the legs. This project will investigate the development and function of the motor circuit used by the adult fruit fly for walking. The use of this model system will help to decipher the genes and neurons required for coordinated locomotion and, therefore, the eventual treatment of motor neuron-related dysfunction resulting from neurodegenerative diseases and aging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS070644-03
Application #
8239896
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Owens, David F
Project Start
2010-04-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$340,641
Indirect Cost
$126,266
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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