Evidence for the involvement of neurotrophins in muscle transdifferentiation and acetylcholine receptor transformation in the esophagus of Myf5(-/-):MyoD(-/-) and NT-3(-/-) embryos.
The primary aim of our study was to determine whether the esophageal innervation (i.e., vagal and enteric) and the skeletal muscle-secreted neurotrophins have a role in smooth-to-skeletal muscle transdifferentiation and in the muscarinic-to-nicotinic acetylcholine receptor type transition. To that end, we used genetically engineered embryos and immunohistochemistry. We found that, in the absence of Myf5 and MyoD, the esophageal muscle cells failed to develop the striated phenotype of acetylcholine receptors. In addition, the development of vagal and enteric innervation was delayed in Myf5(-/-):MyoD(-/-) and NT-3(-/-) mutants, but it was reestablished 2 days before the end of gestation. The smooth muscle cells in the esophagus appeared to be a distinct subpopulation of cells and their ability to transdifferentiate was based on their competence to express neurotrophins and their receptors. Finally, our data suggest a role for NT-3 in the esophageal muscle transdifferentiation.
Reddy
Tyler
T
Dalhousie University, Department of Anatomy and Neurobiology, Halifax, Nova Scotia, Canada.
Kablar
Boris
B
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017615:Enteric Nervous System / Q000196:embryology; D004947:Esophagus / Q000166:cytology / Q000196:embryology* / Q000294:innervation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000196:embryology* / Q000294:innervation; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D051787:Myogenic Regulatory Factor 5; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011950:Receptors, Cholinergic / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014630:Vagus Nerve / Q000196:embryology
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D020933:Neurotrophin 3; D011950:Receptors, Cholinergic; D015534:Trans-Activators