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Abstract
Wnt signaling plays a critical role in craniofacial patterning, as well as tooth and bone development. Rspo2 and Rspo3 are key regulators of Wnt signaling. However, their coordinated function and relative requirement in craniofacial development and odontogensis are poorly understood. We showed that in zebrafish rspo2 and rspo3 are both expressed in osteoprogenitors in the embryonic craniofacial skeleton. This is in contrast to mouse development, where Rspo3 is expressed in osteoprogenitors while Rspo2 expression is not observed. In zebrafish, rspo2 and rspo3 are broadly expressed in the pulp, odontoblasts and epithelial crypts. However, in the developing molars of the mouse, Rspo3 is largely expressed in the dental follicle and alveolar mesenchyme while Rspo2 expression is restricted to the tooth germ. While Rspo3 ablation in the mouse is embryonic lethal, zebrafish rspo3-/- mutants are viable with modest decrease in Meckel’s cartilage rostral length. However, compound disruption of rspo3 and rspo2 revealed synergistic roles of these genes in cartilage morphogenesis, fin development, and pharyngeal tooth development. Adult rspo3−/− zebrafish mutants exhibit a dysmorphic cranial skeleton and decreased average tooth number. This study highlights the differential functions of Rspo2 and Rspo3 in dentocranial morphogenesis in zebrafish and in mouse.
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1 Harvard School of Dental Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
2 Massachusetts General Hospital, Center for Regenerative Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Shriners Hospital for Children, Boston, USA (GRID:grid.415829.3) (ISNI:0000 0004 0449 5362); Harvard Medical School, Department of Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
3 Massachusetts General Hospital, Center for Regenerative Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Shriners Hospital for Children, Boston, USA (GRID:grid.415829.3) (ISNI:0000 0004 0449 5362)
4 Harvard Medical School, Department of Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Boston Children’s Hospital, Department of Orthopedics, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438)
5 Massachusetts General Hospital, Center for Regenerative Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Department of Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
6 Harvard School of Dental Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard Medical School, Department of Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
7 Tufts University School of Dental Medicine, Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Boston, USA (GRID:grid.429997.8) (ISNI:0000 0004 1936 7531)
8 Massachusetts General Hospital, Center for Regenerative Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Shriners Hospital for Children, Boston, USA (GRID:grid.415829.3) (ISNI:0000 0004 0449 5362); Harvard Medical School, Department of Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Massachusetts General Hospital, Division of Plastic and Reconstructive Surgery, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924)