Our overarching research goal is to comprehensively understand the gene regulatory network that directs the development of various motor columns (MCs) in the spinal cord and how each MC contributes to the neural circuitry for locomotion. This proposal is designed to study a MC named PreGanglionic MC (PGC, aka CT for Column of Terni in chick), which is found only in thoracic levels of the spinal cord and contains visceral motor neurons (vMNs) that control the activity of the sympathetic nervous system (SymNS). In sympathetic ganglia, the axons of PGC motor neurons (MNs) form synapse with sympathetic neurons, which then regulate the activity of smooth muscle fibers, cardiac muscles, and glands. Given that vMNs in the PGC control the SymNS, which targets various internal organs, it is tempting to speculate that PGC is not a homogenous cell population and instead consists of multiple subtypes. However, despite recent advances in our generation mechanisms of spinal MCs, little is known about either that specify PGC identity. This study the cellular composition of PGC understanding of the MNs or the molecular will interrogate these two major issues in the field. Our strong preliminary findings led to our hypothesis: PGC MNs have multiple subtypes and Jun is a vital transcription factor in the gene regulatory network that directs fate-specification, differentiation, diversification, cell body migration, and axonal projection of PGC MNs.? To dissect this hypothesis, we will employ an ensemble of cellular, biochemical, genetic and unbiased genome-wide approaches.

Public Health Relevance

In the developing spinal cord, formation of the motor circuitry involves multiple subtypes of motor columns. However, the gene regulation program that directs the initial pool of new-born motor neurons to diversify to different motor columns is poorly understood. This proposal tackles this important issue in neurodevelopment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS111760-01
Application #
9754418
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Riddle, Robert D
Project Start
2019-04-01
Project End
2024-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239