title: Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors.
abstract: Developing skeletal myofibers in vertebrates are intrinsically 'pre-patterned' for motor nerve innervation. However, the intrinsic factors that regulate muscle pre-patterning remain unknown. We found that a functional skeletal muscle dihydropyridine receptor (DHPR, the L-type Ca(2+) channel in muscle) was required for muscle pre-patterning during the development of the neuromuscular junction (NMJ). Targeted deletion of the β1 subunit of DHPR (Cacnb1) in mice led to muscle pre-patterning defects, aberrant innervation and precocious maturation of the NMJ. Reintroducing Cacnb1 into Cacnb1(-/-) muscles reversed the pre-patterning defects and restored normal development of the NMJ. The mechanism by which DHPRs govern muscle pre-patterning is independent of their role in excitation-contraction coupling, but requires Ca(2+) influx through the L-type Ca(2+) channel. Our findings indicate that the skeletal muscle DHPR retrogradely regulates the patterning and formation of the NMJ.
authors: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors: Fujun
authors: F
authors: Chen
authors: Yun
authors: Y
authors: Liu
authors: Yoshie
authors: Y
authors: Sugiura
authors: Paul D
authors: PD
authors: Allen
authors: Ronald G
authors: RG
authors: Gregg
authors: Weichun
authors: W
authors: Lin
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D051927:CD24 Antigen / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000502:physiology*; D002461:Cell Line, Transformed; D055032:Electron Microscope Tomography / Q000379:methods; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000196:embryology*; D009469:Neuromuscular Junction / Q000196:embryology* / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051927:CD24 Antigen; C492923:Cacnb1 protein, mouse; D020746:Calcium Channels, L-Type; C497890:Cd24a protein, mouse; D018398:Homeodomain Proteins; D011978:Receptors, Nicotinic; D014157:Transcription Factors; C084059:Hb9 protein, mouse; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D002118:Calcium