Neurotrophin‐3 and TrkC are expressed in the outflow tract of the developing chicken heart

Bernd, Paulette; Miles, Kathryn; Rozenberg, Inna; Borghjid, Saihan; Kirby, Margaret L.

doi:10.1002/dvdy.20084

Cited by 8 publications

(3 citation statements)

References 30 publications

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“…This could ultimately affect the migration of undifferentiated cells into the conotruncal ridges, resulting in stationary cell growth and consequent thickening of the OFT wall, as seen in TrkC null mice [Youn et al., ]. In addition, NT‐3 and TrkC are present in the OFT of the chicken heart before the arrival of CNCC, suggesting that myocardial cells from the secondary heart field also express TrkC [Bernd et al., ]. Lin et al.…”

Section: Discussionmentioning

confidence: 99%

Mutations inNTRK3Suggest a Novel Signaling Pathway in Human Congenital Heart Disease

et al. 2014

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Congenital heart defects (CHDs) are the most common major birth defects and the leading cause of death from congenital malformations. The etiology remains largely unknown, though genetic variants clearly contribute. In a previous study, we identified a large copy number variant (CNV) that deleted 46 genes in a patient with a malalignment type ventricular septal defect (VSD). The CNV included the gene NTRK3 encoding neurotrophic tyrosine kinase receptor C (TrkC), which is essential for normal cardiogenesis in animal models. To evaluate the role of NTRK3 in human CHDs, we studied 467 patients with related heart defects for NTRK3 mutations. We identified four missense mutations in four patients with VSDs that were not found in ethnically matched controls and were predicted to be functionally deleterious. Functional analysis using neuroblastoma cell lines expressing mutant TrkC demonstrated that one of the mutations (c.278C>T, p.T93M) significantly reduced autophosphorylation of TrkC in response to ligand binding, subsequently decreasing phosphorylation of downstream target proteins. In addition compared to WT, three of the four cell lines expressing mutant TrkC showed altered cell growth in low-serum conditions without supplemental NT-3. These findings suggest a novel pathophysiological mechanism involving NTRK3 in the development of VSDs.

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Section: Discussionmentioning

confidence: 99%

Mutations inNTRK3Suggest a Novel Signaling Pathway in Human Congenital Heart Disease

et al. 2014

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“…Importantly, the status of Runx3 expression is a major determinant of the dorsal-ventral position of termination of sensory axons within the spinal cord. NT3 and TrkC are expressed in the developing heart [89,112]. It was shown that NT-3 was expressed in the ventricular region from E11 to birth in rats.…”

Section: Trkc Transcriptional Regulationmentioning

confidence: 98%

Transcriptional regulation of Trk family neurotrophin receptors

Parada

2006

Cell. Mol. Life Sci.

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The Trk family of neurotrophin receptors plays essential roles in cell fate specification, survival, growth, and differentiation. Their expression patterns are complex and dynamically regulated under many physiological and pathological conditions. However, the molecular mechanisms that control their tissue-specific expression are largely unknown. In this report, we review current knowledge about the transcriptional regulation of Trk receptors.

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“…NTs and their receptors are expressed by the developing heart and vessels (18, 233). Seminal studies performed in global knock-out mice implicated NTs in the in utero development of the heart and the coronary vasculature.…”

Section: Role Of Neurotrophins In Cardiovascular Developmentmentioning

confidence: 99%

Cardiovascular Actions of Neurotrophins

Caporali¹,

Emanueli²

2009

Physiological Reviews

176

180

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Neurotrophins were christened in consideration of their actions on the nervous system and, for a long time, they were the exclusive interest of neuroscientists. However, more recently, this family of proteins has been shown to possess essential cardiovascular functions. During cardiovascular development, neurotrophins and their receptors are essential factors in the formation of the heart and critical regulator of vascular development. Postnatally, neurotrophins control the survival of endothelial cells, vascular smooth muscle cells, and cardiomyocytes and regulate angiogenesis and vasculogenesis, by autocrine and paracrine mechanisms. Recent studies suggest the capacity of neurotrophins, via their tropomyosin-kinase receptors, to promote therapeutic neovascularization in animal models of hindlimb ischemia. Conversely, the neurotrophin low-affinity p75NTRreceptor induces apoptosis of endothelial cells and vascular smooth muscle cells and impairs angiogenesis. Finally, nerve growth factor looks particularly promising in treating microvascular complications of diabetes or reducing cardiomyocyte apoptosis in the infarcted heart. These seminal discoveries have fuelled basic and translational research and thus opened a new field of investigation in cardiovascular medicine and therapeutics. Here, we review recent progress on the molecular signaling and roles played by neurotrophins in cardiovascular development, function, and pathology, and we discuss therapeutic potential of strategies based on neurotrophin manipulation.

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Neurotrophin‐3 and TrkC are expressed in the outflow tract of the developing chicken heart

Cited by 8 publications

References 30 publications

Mutations inNTRK3Suggest a Novel Signaling Pathway in Human Congenital Heart Disease

Mutations inNTRK3Suggest a Novel Signaling Pathway in Human Congenital Heart Disease

Transcriptional regulation of Trk family neurotrophin receptors

Cardiovascular Actions of Neurotrophins

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