A specific requirement for PDGF-C in palate formation and PDGFR-α signaling
A specific requirement for PDGF-C in palate formation and PDGFR-α signaling
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DOI：
10.1038/ng1415
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发表时间：
2004-10-01
期刊：
影响因子：
30.8
通讯作者：
Nagy, A
中科院分区：
文献类型：
--
作者：
Ding, H;Wu, XL;Nagy, A
PDGF-C 是血小板衍生生长因子 (PDGF) 家族的成员，通过 PDGF 受体 (PDGFR) αα 和 Alphata 二聚体发出信号(1,2)。在这里，我们发现 Pdgfc(-/-) 小鼠在围产期因与次级腭裂相关的喂养和呼吸困难而死亡。该表型不如 Pdgfra(-/-) 胚胎严重。 Pdgfc(-/-) Pdgfa(-/-) 胚胎出现面裂、表皮下起泡、肾皮质间充质缺乏、脊柱裂以及骨骼和血管缺陷。因此，两种配体功能的完全丧失反映了PDGFR-α功能的丧失，表明PDGF-A和PDGF-C都通过PDGFR-α发出信号来调节颅面结构、神经管和中胚层器官的发育。我们的结果还表明，PDGF-C 信号传导是腭发育中的一条新途径，不同于且独立于之前所涉及的途径。
PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers(1,2). Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This phenotype was less severe than that of Pdgfra(-/-) embryos. Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs. Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated.