PDGFR-α signaling is critical for tooth cusp and palate morphogenesis
PDGFR-α signaling is critical for tooth cusp and palate morphogenesis
复制标题
DOI：
10.1002/dvdy.20197
复制
发表时间：
2005-01-01
影响因子：
2.5
通讯作者：
Chai, Y
中科院分区：
文献类型：
--
作者：
Xu, X;Bringas, P;Chai, Y
血小板衍生生长因子受体α（PDGFR-α）和PDGF配体是胚胎发育的关键调节因子。虽然PdgfRa在空间上表达于颅神经嵴（CNC）衍生的牙源性间充质中，但PdgfRa缺陷的小鼠是胚胎致死的，使得不可能研究PDGF信号传导在牙齿形态发生过程中调节CNC细胞命运的功能意义。利用肾被膜实验，我们研究了PDGF信号转导在牙齿形态发生中的生物学功能。Pdgfr α和Pdgfa是具体的和一致的表达，分别在CNC衍生的牙源性间充质和牙上皮细胞，在整个牙齿发育的所有阶段，这表明旁分泌功能的PDGF信号调节牙齿形态发生。Pdgfralpha和Pdgfa的高浓度表达模式与牙尖发育相关，表明PDGF信号传导在调节牙尖形成中可能具有功能重要性。Pdgfr α基因的缺失并不影响成牙本质细胞在CNC衍生的牙源性间充质中的正常增殖和分化，但会干扰细胞外基质的形成和牙尖区成牙本质细胞的组织化，导致牙尖生长缺陷。Pdgfr α（-/-）小鼠具有完全腭裂。我们表明，腭裂Pdgfr α突变小鼠的结果从细胞外基质的缺陷内的CNC衍生的腭间充质。一旦腭架在体外紧密接触，突变体腭架的中线上皮仍然具有介导腭融合的功能。总的来说，我们的数据表明，PDGFR α和PDGFA的持续上皮间充质相互作用在牙齿和腭形态发生的关键调节。在颅面发育过程中，PDGFR α信号的中断会干扰牙尖的生长，并干扰腭架的关键延伸。(C)2004 Wiley-Liss，Inc.
Platelet-derived growth factor receptor alpha (PDGFR-alpha) and PDGF ligands are key regulators for embryonic development. Although Pdgfralpha is spatially expressed in the cranial neural crest (CNC)-derived odontogenic mesenchyme, mice deficient for Pdgfra are embryonic lethal, making it impossible to investigate the functional significance of PDGF signaling in regulating the fate of CNC cells during tooth morphogenesis. Taking advantage of the kidney capsule assay, we investigated the biological function of PDGF signaling in regulating tooth morphogenesis. Pdgfralpha and Pdgfa are specifically and consistently expressed in the CNC-derived odontogenic mesenchyme and the dental epithelium, respectively, throughout all stages of tooth development, suggesting a paracrine function of PDGF signaling in regulating tooth morphogenesis. Highly concentrated expression patterns of Pdgfralpha and Pdgfa are associated with the developing dental cusp, suggesting possible functional importance of PDGF signaling in regulating cusp formation. Loss of the Pdgfralpha gene does not affect proper odontoblasts proliferation and differentiation in the CNC-derived odontogenic mesenchyme but perturbs the formation of extracellular matrix and the organization of odontoblast cells at the forming cusp area, resulting in dental cusp growth defect. Pdgfralpha(-/-) mice have complete cleft palate. We show that the cleft palate in Pdgfralpha mutant mice results from an extracellular matrix defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Collectively, our data suggests that PDGFRalpha and PDGFA are critical regulators for the continued epithelial-mesenchymal interaction during tooth and palate morphogenesis. Disruption of PDGFRalpha signaling disturbs the growth of dental cusp and interferes with the critical extension of palatal shelf during craniofacial development. (C) 2004 Wiley-Liss, Inc.