Browsing by Author "Séguin, Cheryle A."

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    Impaired Annulus Fibrosis Development and Vertebral Fusion Cause Severe Scoliosis in Mice with Deficiency of JNK1 and JNK2
    (Elsevier, 2019) Ulici, Veronica; Kelley, Kathryn L.; Longobardi, Lara; McNulty, Margaret A.; Livingston, Eric W.; Bateman, Ted A.; Séguin, Cheryle A.; Louer, Craig R.; Loeser, Richard F.; Anatomy and Cell Biology, IU School of Medicine
    MAP kinases, including JNK, play an important role in the development and function of a large variety of tissues. We analyzed the skeletal phenotype of JNK1 and JNK2 double knockout (dKO) mice (JNK1fl/flCol2-Cre/JNK2-/-) and control genotypes, including single knockouts, at different embryonic and postnatal stages. The JNK1/2 dKO mice displayed a severe scoliotic phenotype that began during development and was grossly apparent around weaning age. Alcian blue staining of embryos (E17.5) showed abnormal fusion of the posterior spinal elements. In the adult mice, fusion of vertebral bodies and of spinous and transverse processes was noted by microCT, Alcian blue/Alizarin red stain and histology. The long bones developed normally and histological sections of the growth plate and articular cartilage did not reveal significant abnormalities. Histological sections of the vertebral column at E15.5 and E17.5 revealed an abnormal organization of the annulus fibrosus in the dKOs, with chondrocyte-like cells and fusion of dorsal processes. Spinal sections in 10-week–old dKO mice showed replacement of intervertebral disc structures (annulus fibrosus and nucleus pulposus) by cartilage and bone tissues, with cells staining for markers of hypertrophic chondrocytes including collagen X and Runx2. These findings demonstrate a requirement for both JNK1 and JNK2 in the normal development of the axial skeleton with loss of JNK signaling resulting in abnormal endochondral bone formation and subsequent severe scoliosis.
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    Impaired Annulus Fibrosus Development and Vertebral Fusion Cause Severe Scoliosis in Mice with Deficiency of c-Jun NH2-Terminal Kinases 1 and 2
    (Elsevier, 2019-04) Ulici, Veronica; Kelley, Kathryn L.; Longobardi, Lara; McNulty, Margaret A.; Livingston, Eric W.; Bateman, Ted A.; Séguin, Cheryle A.; Louer, Craig R.; Loeser, Richard F.; Anatomy and Cell Biology, School of Medicine
    Mitogen-activated protein kinases, including c-Jun NH2-terminal kinase (JNK), play an important role in the development and function of a large variety of tissues. The skeletal phenotype of JNK1 and JNK2 double-knockout (dKO) mice (JNK1fl/flCol2-Cre/JNK2−/−) and control genotypes were analyzed at different embryonic and postnatal stages. JNK1/2 dKO mice displayed a severe scoliotic phenotype beginning during development that was grossly apparent around weaning age. Alcian blue staining at embryonic day 17.5 showed abnormal fusion of the posterior spinal elements. In adult mice, fusion of vertebral bodies and of spinous and transverse processes was noted by micro–computed tomography, Alcian blue/Alizarin red staining, and histology. The long bones developed normally, and histologic sections of growth plate and articular cartilage revealed no significant abnormalities. Histologic sections of the vertebral column at embryonic days 15.5 and 17.5 revealed an abnormal organization of the annulus fibrosus in the dKOs, with chondrocyte-like cells and fusion of dorsal processes. Spinal sections in 10-week–old dKO mice showed replacement of intervertebral disk structures (annulus fibrosus and nucleus pulposus) by cartilage and bone tissues, with cells staining for markers of hypertrophic chondrocytes, including collagen X and runt-related transcription factor 2. These findings demonstrate a requirement for both JNK1 and JNK2 in the normal development of the axial skeleton. Loss of JNK signaling results in abnormal endochondral bone formation and subsequent severe scoliosis.