During embryonic development, the heart becomes innervated by sympathetic nerves, which control heart rate and contractility. Sympathetic nerve extend along blood vessels to reach their targets, in what is called "neurovascular congruency", but virtually nothing is known of how these axons are instructed to reach the heart in order to establish a precise circuitry. New observations described in this proposal lead to a model in which endothelin signaling from specific vascular components is a critical guidance mechanism for sympathetic axons to take appropriate routes in order to reach the heart. In this application, using both in vivo and in vitro assays, I propose experiments to address the spatial and functional role of specific components of endothelin signaling in cardiac axon guidance. I approach this strategy within a developmental context that coordinates neuronal outgrowth with cardiovascular cell lineage and morphogenesis.

Public Health Relevance

The heart is innervated by sympathetic and parasympathetic divisions of the autonomic nervous system, which is essential in regulating cardiovascular responses to emotion and stress. Autonomic imbalance results in deadly consequences such as cardiac arrhythmia. This project addresses how sympathetic axons reach and maintain normal function of the heart.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS083265-02
Application #
8670042
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Riddle, Robert D
Project Start
2013-06-15
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$350,830
Indirect Cost
$134,268
Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
052277936
City
Los Angeles
State
CA
Country
United States
Zip Code
90027