Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis
Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis
复制标题
DOI：
10.1152/ajplung.90550.2008
复制
发表时间：
2010-01-01
影响因子：
4.9
通讯作者：
Egan, Sean E.
中科院分区：
文献类型：
--
作者：
Xu, Keli;Nieuwenhuis, Erica;Egan, Sean E.
许坤，Nieuwenhuis E, Cohen BL，王伟，Canty AJ, Danska JS, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM，于立新，Sled JG, Gridley T, Egan SE。疯子边缘介导的Notch信号是肺泡形成所必需的。[J] .中国生物医学工程学报，2016,31(4):557 - 557。首次发表于2009年11月6日；doi: 10.1152 / ajplung.90550.2008。远端肺的发育是通过肌成纤维细胞、上皮细胞和毛细血管的协调诱导发生的。Lunatic Fringe （lfg）是一种β (1-3) n -乙酰氨基葡萄糖转移酶，可修饰Notch受体，促进其被δ样（Dll1/4）配体激活。lgf在囊状细胞发育过程中在远端肺中表达，在这种情况下，该基因的缺失会损害肌成纤维细胞的分化和肺泡形成。在Notch2（β -geo/+）和Notch3（β -geo/ β -geo）复合突变体小鼠中观察到类似的缺陷，但在Notch2（β -geo/+）和Notch3（β -geo/ β -geo）单突变体小鼠中没有观察到类似的缺陷。最后，为了直接测试Notch信号在体内肌成纤维细胞分化中的作用，我们使用了ROSA26-rtTA(/+)；tetO-CRE / +;RBPJ kappa（flox/flox）诱导突变小鼠的研究表明，胚胎发育后期典型Notch信号的破坏阻止了远端肺间充质细胞平滑肌肌动蛋白的诱导。综上所述，这些结果表明，lfg可以增强肌成纤维细胞前体细胞中的Notch信号，从而协调肺泡分隔所需的肌成纤维细胞的分化和动员。
Xu K, Nieuwenhuis E, Cohen BL, Wang W, Canty AJ, Danska JS, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM, Yu LX, Sled JG, Gridley T, Egan SE. Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol 298: L45-L56, 2010. First published November 6, 2009; doi:10.1152/ajplung.90550.2008.-Distal lung development occurs through coordinated induction of myofibroblasts, epithelial cells, and capillaries. Lunatic Fringe (Lfng) is a beta(1-3) N-acetylglucosamine transferase that modifies Notch receptors to facilitate their activation by Delta-like (Dll1/4) ligands. Lfng is expressed in the distal lung during saccular development, and deletion of this gene impairs myofibroblast differentiation and alveogenesis in this context. A similar defect was observed in Notch2(beta-geo/+)Notch3(beta-geo/beta-geo) compound mutant mice but not in Notch2(beta-geo/+) or Notch3(beta-geo/beta-geo) single mutants. Finally, to directly test for the role of Notch signaling in myofibroblast differentiation in vivo, we used ROSA26-rtTA(/+); tetO-CRE/+; RBPJ kappa(flox/flox) inducible mutant mice to show that disruption of canonical Notch signaling during late embryonic development prevents induction of smooth muscle actin in mesenchymal cells of the distal lung. In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation.