Jagged1 is essential for osteoblast development during maxillary ossification.
Maxillary hypoplasia occurs due to insufficient maxillary intramembranous ossification, leading to poor dental occlusion, respiratory obstruction and cosmetic deformities. Conditional deletion of Jagged1 (Jag1) in cranial neural crest (CNC) cells using Wnt1-cre; Jagged1(f/f) (Jag1CKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using μCT evaluation. Jag1CKO maxillas revealed altered collagen deposition, delayed ossification, and reduced expression of early and late determinants of osteoblast development during maxillary ossification. In vitro bone cultures on Jag1CKO mouse embryonic maxillary mesenchymal (MEMM) cells demonstrated decreased mineralization that was also associated with diminished induction of osteoblast determinants. BMP receptor expression was dysregulated in the Jag1CKO MEMM cells suggesting that these cells were unable to respond to BMP-induced differentiation. JAG1-Fc rescued in vitro mineralization and osteoblast gene expression changes. These data suggest that JAG1 signaling in CNC-derived MEMM cells is required for osteoblast development and differentiation during maxillary ossification.
Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: cynthia.r.allison@vanderbilt.edu.
Cynthia R
CR
Hill
Department of Orthopedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: masato.yuasa@vanderbilt.edu.
Masato
M
Yuasa
Department of Orthopedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: jon.schoenecker@vanderbilt.edu.
Jonathan
J
Schoenecker
Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: steven.goudy@vanderbilt.edu.
Steven L
SL
Goudy
D000818:Animals; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008437:Maxilla / Q000000981:diagnostic imaging / Q000196:embryology / Q000378:metabolism* / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D018345:Mice, Knockout; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D010159:Palate / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D055114:X-Ray Microtomography
D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011961:Receptors, Fc; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D002118:Calcium
Cranial neural crest; Jagged1; Maxillary hypoplasia; Mesenchymal cells; Ossification; Osteoblasts