title: CLIPR-59: a protein essential for neuromuscular junction stability during mouse late embryonic development.
abstract: CLIPR-59 is a new member of the cytoplasmic linker proteins (CLIP) family mainly localized to the trans-Golgi network. We show here that Clipr-59 expression in mice is restricted to specific pools of neurons, in particular motoneurons (MNs), and progressively increases from embryonic day 12.5 (E12.5) until the first postnatal days. We generated a Clipr-59 knockout mouse model that presents perinatal lethality due to respiratory defects. Physiological experiments revealed that this altered innervation prevents the normal nerve-elicited contraction of the mutant diaphragm that is reduced both in amplitude and fatigue-resistance at E18.5, despite unaffected functional muscular contractility. Innervation of the mutant diaphragm is not altered until E15.5, but is then partially lost in the most distal parts of the muscle. Ultrastructural observations of neuromuscular junctions (NMJs) in the distal region of the diaphragm reveal a normal organization, but a lower density of nerve terminals capped by terminal Schwann cells in E18.5 mutant when compared with control embryos. Similar defects in NMJ stability, with a hierarchy of severity along the caudo-rostral axis, are also observed in other muscles innervated by facial and spinal MNs in Clipr-59 mutant mice. Clipr-59 deficiency therefore affects axon maintenance but not axon guidance toward muscle targets. Thus, CLIPR-59 is involved in the stabilization of specific motor axons at the NMJ during mouse late embryogenesis and its role is crucial for mouse perinatal development.
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS UMR 8104, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Couesnon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Offner
authors.forename: Véronique
authors.initials: V
authors.lastname: Bernard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaverot
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Backer
authors.forename: Ariane
authors.initials: A
authors.lastname: Dimitrov
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.forename: Jordi
authors.initials: J
authors.lastname: Molgó
authors.forename: Evelyne
authors.initials: E
authors.lastname: Bloch-Gallego
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics* / Q000502:physiology; D005260:Female; D005865:Gestational Age; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009469:Neuromuscular Junction / Q000196:embryology* / Q000235:genetics* / Q000502:physiology*; D011247:Pregnancy; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism
chemical_list: C539981:ClipR-59 protein, mouse; D008869:Microtubule-Associated Proteins