Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development

  title={Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development},
  author={Michael J. Donovan and Rebecca Hahn and Lino Tessarollo and Barbara L. Hempstead},
  journal={Nature Genetics},
Neurotrophin 3 (Nt3) is one of five neurotrophin growth factors which shape the development of the nervous system by regulating neuronal survival and differentiation. Peripheral neuronal subpopulations expressing the TrkC receptor tyrosine kinase respond to Nt3 with enhanced survival, mitogenesis or cell migration1–3 and these neurons are lost in homozygous Nt3 null (−/−) mutant mice4–7. The unexplained perinatal lethality in the Nt3 −/− mice, however, suggests a wider function for this… 
Inactivation of one copy of the mouse neurotrophin-3 gene induces cardiac sympathetic deficits.
Deletion of one copy of the NT3 gene translates into anatomical, biochemical, and functional deficits in cardiac sympathetic innervation of postnatal mice, thereby indicating a gene-dosage effect for theNT3 gene.
Trk C receptor signaling regulates cardiac myocyte proliferation during early heart development in vivo.
It is demonstrated that endogenous NT-3:trk C signaling regulates cardiac myocytes proliferation during cardiac looping and the establishment of ventricular trabeculation but that myocyte proliferation becomesNT-3 independent during the second week of embryogenesis.
Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development
A detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75NTR is reported.
Investigation of neuromuscular abnormalities in neurotrophin‐3‐deficient mice
The results indicate that a reduction in NT‐3 availability during development impairs motor nerve terminal maturation and synaptic vesicle recycling and leads to a reduce in muscle fiber diameter.
Neurotrophin-3 Is Required for the Survival–Differentiation of Subsets of Developing Enteric Neurons
The observations indicate that NT-3 is required for the normal development of the ENS, and a neuropoietic cytokine (CNTF) interacted withNT-3 in vitro, and if applied sequentially, compensated for NT- 3 withdrawal.
A comprehensive analysis of neurotrophins and neurotrophin tyrosine kinase receptors expression during development of zebrafish
This study unveils new expression domains in the developing embryo, confirms those previously known, and shows that ntf and ntrk genes have different degrees of cell‐ and tissue‐type specificity.
Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis.
Neuronal counts of sensory ganglia in the trkC mutant mice reveal less severe losses than those in NT-3 null mutant mice, strongly suggesting thatNT-3, in vivo, may signal through receptors other thantrkC.


Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons.
Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development.
Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system
The results indicate that the trkC gene is widely expressed in the three identified branches of the mammalian nervous system and appears to correlate with the expression of NT-3, its cognate ligand.
Severe sensory and sympathetic deficits in mice lacking neurotrophin-3
It is reported that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations and motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally.
Expression of trkC receptor mRNA during development of the avian nervous system.
Results support the notion that the NT-3-TrkC complex mediates diverse functions during neural development, and report that trkC-encoding transcripts are expressed in the CNS primordium in several spatiotemporal distinct waves.
trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues.
Insight is provided into the role of Trk-family receptors and nerve growth factor-related neurotrophins during development and suggest that, in addition to regulating neuronal survival and differentiation, the neurotrophin/Trk receptor system may have broader physiological effects.
Coexpression of mRNAs for NGF, BDNF, and NT-3 in the cardiovascular system of the pre- and postnatal rat
The expression of NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs was examined in whole rat embryos and in the heart and great vessels of postnatal and adult rats, using
Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury.
A new functional role is defined for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration, as well as their cognate receptors, the trk tyrosine kinases, in human and rat vascular smoother muscle cells in vivo.