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 #
5R01NS070644-05
Application #
8638819
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Owens, David F
Project Start
2010-04-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
5
Fiscal Year
2014
Total Cost
$339,795
Indirect Cost
$127,564
Name
Columbia University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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
Mann, Richard S (2014) Neuroscience. The Michael Jackson fly. Science 344:48-9
Mendes, C├ęsar 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
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