title: Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation.
abstract: Neuromuscular junction formation requires proper interaction between motoneurons and muscle cells. β-Catenin (Ctnnb1) in muscle is critical for motoneuron differentiation; however, little is known about the relevant retrograde signal. In this paper, we dissected which functions of muscle Ctnnb1 are critical by an in vivo transgenic approach. We show that Ctnnb1 mutant without the transactivation domain was unable to rescue presynaptic deficits of Ctnnb1 mutation, indicating the involvement of transcription regulation. On the other hand, the cell-adhesion function of Ctnnb1 is dispensable. We screened for proteins that may serve as a Ctnnb1-directed retrograde factor and identified Slit2. Transgenic expression of Slit2 specifically in the muscle was able to diminish presynaptic deficits by Ctnnb1 mutation in mice. Slit2 immobilized on beads was able to induce synaptophysin puncta in axons of spinal cord explants. Together, these observations suggest that Slit2 serves as a factor utilized by muscle Ctnnb1 to direct presynaptic differentiation.
authors.affiliation: Department of Neurobiology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Arnab
authors.identifier: http://orcid.org/0000-0001-6850-0894
authors.initials: A
authors.lastname: Barik
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Chengyong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bowman
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Anupama
authors.initials: A
authors.lastname: Sathyamurthy
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Thiri W
authors.initials: TW
authors.lastname: Lin
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032342:Muscle Cells / Q000502:physiology; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000098552:Slit Homolog 2 Protein
chemical_list: C495267:CTNNB1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D051176:beta Catenin; D000098552:Slit Homolog 2 Protein
keywords: Ctnnb1; NMJ; Wnt; mouse; neuroscience