Wnt5a participates in distal lung morphogenesis
Wnt5a participates in distal lung morphogenesis
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DOI：
10.1006/dbio.2002.0729
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发表时间：
2002-08-01
影响因子：
2.7
通讯作者：
Minoo, P
中科院分区：
文献类型：
--
作者：
Li, CG;Xiao, J;Minoo, P
脊椎动物器官的三维模式化的整体机制中的操作相似性正变得越来越明显。许多关键介质，如FGF、BMP和音刺猬，参与许多器官的组织，包括肺，其表现出确定的近端（P-D）极性。最近，Wnt 5a是参与细胞增殖、分化和器官发生的无翅信号分子家族的成员，被证明是脊椎动物肢体的生长和P-D形态发生的基础。在目前的研究中，我们发现Wnt 5a在小鼠肺中表达，并在肺远端形态发生中起重要作用。对携带Wnt 5a基因座靶向破坏的小鼠中的突变表型的分析显示远端肺形态发生的明显异常，如气管的明显截短和远端呼吸道的过度扩张所表现的。面对WNT 5a活性缺失，Wnt 5a（-/-）肺的上皮细胞和间充质细胞区室都表现出细胞增殖增加。突变体肺的整体结构的特征在于远端气道的过度扩张和肺成熟的抑制，如由增厚的囊间结缔组织的持续存在所反映的。突变体肺中WNT 5a活性的缺失导致Fgf-10、Bmp 4、Shh及其受体Ptc的表达增加，从而提高了WNT 5a、FGF-10、BMP 4和SHH信号传导途径在功能上相互作用的可能性。(C)2002 Elsevier Science（美国）。
Operational parallels in overall mechanisms of three-dimensional patterning of vertebrate organs are becoming increasingly apparent. Many key mediators, such as FGFs, BMPs, and sonic hedgehog, participate in organization of a number of organs, including the lungs, which exhibit a defined proximodistal (P-D) polarity. Recently, Wnt5a a member of the wingless family of signaling molecules involved in cell proliferation, differentiation, and organogenesis, was shown to underlie the outgrowth and P-D morphogenesis of the vertebrate limb. In the current study, we show that Wnt5a is expressed in the mouse lung and plays an important role in lung distal morphogenesis. Analysis of the mutant phenotype in mice carrying a targeted disruption of the Wnt5a locus shows distinct abnormalities in distal lung morphogenesis as manifested by distinct truncation of the trachea and overexpansion of the distal respiratory airways. in the face of deleted WNT5a activity, both epithelial and mesenchymal cell compartments of the Wnt5a(-/-) lungs exhibit increased cell proliferation. The overall architecture of the mutant lungs is characterized by overexpansion of the distal airways and inhibition of lung maturation as reflected by persistence of thickened intersaccular interstitium. Absence of WNT5a activity in the mutant lungs leads to increased expression of Fgf-10, Bmp4, Shh, and its receptor Ptc, raising the possibility that WNT5a, FGF-10, BMP4, and SHH signaling pathways are functionally interactive. (C) 2002 Elsevier Science (USA).