内胚层
FGF10型
生物
间充质
形态发生
细胞生物学
成纤维细胞生长因子
骨形态发生蛋白4
胚胎干细胞
胚胎
遗传学
基因
受体
作者
Molly Weaver,N. Ray Dunn,Brigid L.M. Hogan
出处
期刊:Development
[The Company of Biologists]
日期:2000-06-15
卷期号:127 (12): 2695-2704
被引量:501
标识
DOI:10.1242/dev.127.12.2695
摘要
ABSTRACT Morphogenesis of the mouse lung involves reciprocal interactions between the epithelial endoderm and the surrounding mesenchyme, leading to an invariant early pattern of branching that forms the basis of the respiratory tree. There is evidence that Fibroblast growth factor 10 (Fgf10) and Bone Morphogenetic Protein 4 (Bmp4), expressed in the distal mesenchyme and endoderm, respectively, play important roles in branching morphogenesis. To examine these roles in more detail, we have exploited an in vitro culture system in which isolated endoderm is incubated in MatrigelTM substratum with Fgf-loaded beads. In addition, we have used a Bmp4lacZ line of mice in which lacZ faithfully reports Bmp4 expression. Analysis of lung endoderm in vivo shows a dynamic pattern of Bmp4lacZ expression during bud outgrowth, extension and branching. In vitro, Fgf10 induces both proliferation and chemotaxis of isolated endoderm, whether it is derived from the distal or proximal lung. Moreover, after 48 hours, Bmp4lacZ expression is upregulated in the endoderm closest to the bead. Addition of 30-50 ng/ml of exogenous purified Bmp4 to the culture medium inhibits Fgf-induced budding or chemotaxis, and inhibits overall proliferation. By contrast, the Bmp-binding protein Noggin enhances Fgf-induced morphogenesis. Based on these and other results, we propose a model for the combinatorial roles of Fgf10 and Bmp4 in branching morphogenesis of the lung.
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