Apoptosis in murine calvarial bone and suture development.
To study the possible role of apoptosis in calvarial bone and suture development, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) was performed on whole mount and sectioned calvariae from mice aged between E14 and P6. We also analyzed by in situ hybridization the expression of Msx2, Bmp4 and Bmp7 genes, which are known to act in conserved signaling pathways leading to apoptosis. We found TUNEL-positive cells from E16 onwards in the calvarial bones, intervening sutures and fontanelles. TUNEL-positive osteoblasts and preosteoblasts were identified at or close to the osteogenic fronts, areas of intense osteogenic activity, with TUNEL-positive mesenchymal cells located in the midsutural mesenchyme. TUNEL-positive osteoclasts and osteocytes were also observed in a sporadic fashion, as well as TUNEL-positive dural cells. Msx2 was expressed in the sutural mesenchyme and the dura mater. Bmp4 was expressed in the developing bone, underlying dura mater, the osteogenic fronts, and also weakly in the sutural mesenchyme. Bmp7 was detected at the same locations as Bmp4 but with noticeably stronger intensity in the meninges and overlying epidermis. We propose that this apoptosis is part of normal suture development, and is integral to the balance between bone formation and resorption, so that abnormal apoptosis may lead to premature (Craniosynostosis) or delayed (Cleidocranial dysplasia) suture closure.
Rice
D P
DP
Department of Pedodontics and Orthodontics, Institute of Dentistry, University of Helsinki, Finland. Rice@operoni.helsinki.fi
Kim
H J
HJ
Thesleff
I
I
D000818:Animals; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics; D002973:Cleidocranial Dysplasia / Q000235:genetics; D003393:Cranial Sutures / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D003398:Craniosynostoses / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004388:Dura Mater / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008578:Meninges / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012886:Skull / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D016212:Transforming Growth Factor beta / Q000235:genetics
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D016212:Transforming Growth Factor beta