title: Mutations in the Notch pathway alter the patterning of multifidus.
abstract: Clinical studies have suggested that defects in the epaxial muscles, particularly multifidus, may contribute to the etiology of idiopathic scoliosis. While the epaxial muscles and the vertebrae derive from the same embryonic segmentation process, the mechanisms that pattern the multisegmental back muscles are still unclear. The process of segmentation is regulated by the Notch signaling pathway, and mutations in the modulators delta-like 3 (Dll3) and lunatic fringe (Lfng) are genetic models for spinal disorders such as scoliosis. Osteological defects have been characterized in these genetic models, but myological phenotypes have not previously been studied. We analyzed the multifidus muscle in the mouse (Mus musculus) and observed intriguing changes in the cranio-caudal borders of multifidus in Dll3 and Lfng models. Statistical analysis did not find a significant association between the majority of the multifidus anomalies and the vertebral defects, suggesting a previously unappreciated role for Notch signaling in patterning epaxial muscle groups. These findings indicate an additional mechanism by which DLL3 and LFNG may play a role in the etiology of human idiopathic scoliosis.
authors.affiliation: Department of Basic Medical Sciences, The University of Arizona College of Medicine-Phoenix, USA. rfisher@email.arizona.edu
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Fisher
authors.forename: Heather F
authors.initials: HF
authors.lastname: Smith
authors.forename: Kenro
authors.initials: K
authors.lastname: Kusumi
authors.forename: Erica E
authors.initials: EE
authors.lastname: Tassone
authors.forename: Alan
authors.initials: A
authors.lastname: Rawls
authors.forename: Jeanne
authors.initials: J
authors.lastname: Wilson-Rawls
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016695:Glycosyltransferases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000002:abnormalities* / Q000502:physiology; D009154:Mutation / Q000235:genetics; D051880:Receptors, Notch / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D012600:Scoliosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C496666:DLL3 protein, human; C511877:Dll3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D016695:Glycosyltransferases; C498393:LFNG protein, human; C498392:Lfng protein, mouse