Our previous studies demonstrate that the pattern of large-diameter coronary veins influences the pattern of sympathetic innervation in the developing heart (Nam et al. Development, 2013). At a mechanistic level, sequential expression of NGF in the subepicardial venous VSMCs and myocardial arterial VSMCs determines the stereotypical pattern of sympathetic innervation in the developing heart. We further explore the regulatory mechanisms by which coronary VSMCs guide patterns of sympathetic innervation and tackle two intriguing unresolved questions in neuronal development: how does guidance factor expression shift from central to peripheral blood vessels (e.g. from subepicaridial veins to myocardial arteries) in parallel with axon extension along these vessels; what determines the choice of either innervation to blood vessels or axon extension along blood vessels en route to their final targets. We are also developing a tissue-clearing method to map the physical patterns of sympathetic and parasympathetic nerve branching in the myocardium and detail the architecture of the conduction system including the His-Purkinje system. These studies will provide a molecular mechanistic framework for the developmental program underlying vascular control of neuronal guidance and innervation patterns. We are engaged in a new project for studying the role of abnormal angiogenesis in single ventricle (SV) congenital heart disease patients who often form aortopulmonary collateral (APC) vessels. Under a close collaboration with Division of Pediatric Cardiology, Children's National Heart Institute, we have provided the first study to simultaneously correlate angiography with plasma angiogenic factor levels and in vitro angiogenic activity in SV patients with APCs (Sandeep et al. J Thorac Cardiovasc Surg. 2016)
| Sandeep, Nefthi; Uchida, Yutaka; Ratnayaka, Kanishka et al. (2016) Characterizing the angiogenic activity of patients with single ventricle physiology and aortopulmonary collateral vessels. J Thorac Cardiovasc Surg 151:1126-35.e2 |
| Liu, Zhihui; Li, Wenling; Ma, Xuefei et al. (2014) Essential role of the zinc finger transcription factor Casz1 for mammalian cardiac morphogenesis and development. J Biol Chem 289:29801-16 |
| Mukouyama, Yoh-suke (2014) Vessel-dependent recruitment of sympathetic axons: looking for innervation in all the right places. J Clin Invest 124:2855-7 |
| Nam, Joseph; Onitsuka, Izumi; Hatch, John et al. (2013) Coronary veins determine the pattern of sympathetic innervation in the developing heart. Development 140:1475-85 |
| Mukouyama, Yoh-suke; James, Jennifer; Nam, Joseph et al. (2012) Whole-mount confocal microscopy for vascular branching morphogenesis. Methods Mol Biol 843:69-78 |
