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.
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.
| Patterson, Michaela; Barske, Lindsey; Van Handel, Ben et al. (2017) Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nat Genet 49:1346-1353 |
| Shen, Hua; Cavallero, Susana; Estrada, Kristine D et al. (2015) Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion. Cardiovasc Res 105:271-8 |
| Suo, Dong; Park, Juyeon; Young, Samuel et al. (2015) Coronin-1 and calcium signaling governs sympathetic final target innervation. J Neurosci 35:3893-902 |
| Manousiouthakis, Eleana; Mendez, Monica; Garner, Madeline C et al. (2014) Venous endothelin guides sympathetic innervation of the developing mouse heart. Nat Commun 5:3918 |
