title: Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis.
abstract: Maxillofacial dysmorphogenesis is found in 5% of the population. To begin to understand the mechanisms required for maxillofacial morphogenesis, we employed the inhibitors of the differentiation 2 (Id2) knock-out mouse model, in which Id proteins, members of the regulator of basic helix-loop-helix (bHLH) transcription factors, modulate cell proliferation, apoptosis, and differentiation. We now report that spatially-restricted growth defects are localized at the skull base of Id2 KO mice. Curiously, at birth, neither the mutant Id2 KO nor wild-type (WT) mice differed, based upon cephalometric and histological analyses of cranial base synchondroses. In postnatal week 2, a narrower hypertrophic zone and an inhibited proliferative zone in presphenoid synchondrosis (PSS) and spheno-occipital synchondrosis (SOS) with maxillary hypoplasia were identified in the Id2 mutant mice. Complementary studies revealed that exogenous bone morphogenetic proteins (BMPs) enhanced cartilage growth, matrix deposition, and chondrocyte proliferation in the WT but not in the mutant model. Id2-deficient chondrocytes expressed more Smad7 transcripts. Based on our results, we assert that Id2 plays an essential role, acting downstream of BMP signaling, to regulate cartilage formation at the postnatal stage by enhancing BMP signals through inhibiting Smad7 expression. As a consequence, abnormal endochondral ossification was observed in cranial base synchondroses during the postnatal growth period, resulting in the clinical phenotype of maxillofacial dysmorphogenesis.
authors: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Japan.
authors: Tomoko
authors: T
authors: Sakata-Goto
authors: Katsu
authors: K
authors: Takahashi
authors: Honoka
authors: H
authors: Kiso
authors: Boyen
authors: B
authors: Huang
authors: Hiroko
authors: H
authors: Tsukamoto
authors: Mitsuru
authors: M
authors: Takemoto
authors: Tatsunari
authors: T
authors: Hayashi
authors: Manabu
authors: M
authors: Sugai
authors: Takashi
authors: T
authors: Nakamura
authors: Yoshifumi
authors: Y
authors: Yokota
authors: Akira
authors: A
authors: Shimizu
authors: Harold
authors: H
authors: Slavkin
authors: Kazuhisa
authors: K
authors: Bessho
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D008437:Maxilla / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019291:Skull Base / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D051906:Smad7 Protein; C497807:Smad7 protein, mouse