AChR channel conversion and AChR-adjusted neuronal survival during embryonic development.
We generated knock-in mice that express GFP-labeled embryonic-type acetylcholine receptors (AChR) to follow postsynaptic differentiation and innervation during embryonic development and to visualize the postnatally occurring channel conversion from embryonic- to adult-type AChR. The dynamics of AChRgamma/AChRepsilon conversion at the neuromuscular junction indicates that muscle-specific programs of receptor subunit gene transcription control AChR replacement. While conversion proceeds from peripheral to central regions for individual endplates, it does not occur simultaneously for all endplates. Although GFP-labeled receptors were expressed at reduced levels, the localization of postsynaptic sites and synapse formation was not noticeably altered. However, these alterations correlated with a striking reduction of motoneuron programmed cell death, transient increase of neurite growth and axon branching. This animal model refines the view on reciprocal neuromuscular signaling and suggests that motoneuron survival and axon branching are directly regulated by AChR function to enable optimal innervation and timing of neurally evoked muscle contraction.
Yampolsky
Pessah
P
Max-Planck-Institute for Medical Research, Department of Cell Physiology, Jahnstrasse 29, D-69120 Heidelberg, Germany.
Gensler
Sven
S
McArdle
Joseph
J
Witzemann
Veit
V
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D002038:Bungarotoxins / Q000378:metabolism; D002470:Cell Survival; D004622:Embryo, Mammalian; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009130:Muscle, Smooth / Q000196:embryology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000235:genetics; D011950:Receptors, Cholinergic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000378:metabolism
D002038:Bungarotoxins; C502449:Chrne protein, mouse; D008164:Luminescent Proteins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D000110:Acetylcholinesterase