The expression and function of netrin-4 in murine ocular tissues.
The expression and function of netrin-4 in murine ocular tissues.
复制标题
DOI：
10.1016/j.exer.2012.01.007
复制
发表时间：
2012-03
影响因子：
3.4
通讯作者：
Brunken, William J.
中科院分区：
文献类型：
--
作者：
Li, Yong N.;Pinzon-Duarte, German;Dattilo, Michael;Claudepierre, Thomas;Koch, Manuel;Brunken, William J.
Netrin-4是netrin家族的成员，是胚胎发育的有效调节剂。在病理性血管生成中促进神经突延伸并调节肺气道分支、血管发生模式和内皮增殖。netrin-4表达的最初表征集中于上皮来源的器官（肾、肺和唾液腺）和中枢神经系统。眼发育是研究netrin-4表达和功能的理想系统，因为它涉及外胚层（角膜、透镜和视网膜）和中胚层（巩膜和脉络膜）衍生物，并且具有广泛且充分表征的血管生成过程。Netrin-4在所有眼组织中表达。它是透镜和角膜的基底膜以及视网膜的所有三种基底膜（内界膜、血管基底膜和布鲁赫膜）的主要成分。Netrin-4差异性地沉积在血管基底膜中，在动脉侧具有更强烈的抗Netrin-4反应性。视网膜微循环也表达netrin-4。为了测试netrin-4在体内的功能，我们产生了缺乏Ntn 4表达的常规小鼠。角膜、透镜和视网膜中的基底膜形成未被netrin-4缺失破坏，表明netrin-4不是这些基底膜的主要结构组分。在Ntn 4纯合无效（Ntn 4 −/−）角膜中，角膜的整体形态以及上皮、基质和内皮分层是正常的;然而，上皮细胞增殖增加。在Ntn 4 −/−视网膜中，神经发生似乎正常进行，视网膜分层也是如此。在Ntn 4 −/−视网膜中，视网膜神经节细胞靶向是完整的，尽管轴突成束有轻微缺陷。在Ntn 4 −/−视网膜的视网膜血管系统中，星形胶质细胞和血管系统的分布模式在很大程度上是正常的，除了在深毛细血管丛中增加的分支，这表明netrin-4可能作为血管生成的负调节剂。这些数据综合起来表明，netrin-4是体内角膜上皮细胞增殖和视网膜血管分支的负调节剂，而netrin-4可能与netrin家族的其他成员在其他眼组织发育中是多余的。Ntn 4 −/−小鼠可以作为一个很好的模型，在其中研究netrins在视网膜和角膜的病理生物学血管重塑的体内作用。
Netrin-4, a member of the netrin family, is a potent regulator of embryonic development. It promotes neurite extension and regulates pulmonary airway branching, vasculogenesis patterning, and endothelial proliferation in pathological angiogenesis. The initial characterization of netrin-4 expression was focused on epithelial-derived organs (kidney, lung and salivary gland) and the central nervous system. Ocular development is an ideal system to study netrin-4 expression and function, as it involves both ectodermal (cornea, lens and retina) and mesodermal (sclera and choroid) derivatives and has an extensive and well-characterized angiogenic process. Netrin-4 is expressed in all ocular tissues. It is a prominent component of the basement membranes of the lens and cornea, as well as all three basement membranes of the retina: the inner limiting membrane, vascular basement membranes, and Bruch’s membrane. Netrin-4 is differentially deposited in vascular basement membranes, with more intense anti-netrin-4 reactivity on the arterial side. The retinal microcirculation also expresses netrin-4. In order to test the function of netrin-4 in vivo, we generated a conventional mouse lacking Ntn4 expression. Basement membrane formation in the cornea, lens and retina is undisrupted by netrin-4 deletion, demonstrating that netrin-4 is not a major structural component of these basement membranes. In the Ntn4 homozygous null (Ntn4−/−) cornea, the overall morphology of the cornea, as well as the epithelial, stromal and endothelial stratification are normal; however, epithelial cell proliferation is increased. In the Ntn4−/− retina, neurogenesis appears to proceed normally, as does retinal lamination. In the Ntn4−/− retina, retinal ganglion cell targeting is intact, although there are minor defects in axon fasciculation. In the retinal vasculature of the Ntn4−/− retina, the distribution patterns of astrocytes and the vasculature are largely normal, with the possible exception of increased branching in the deep capillary plexus, suggesting that netrin-4 may act as a negative regulator of angiogenesis. These data, taken together, suggest that netrin-4 is a negative regulator of corneal epithelial cell proliferation and retinal vascular branching in vivo, whereas netrin-4 may be redundant with other members of the netrin family in other ocular tissue development. Ntn4−/− mice may serve as a good model in which to study the role of netrins in vivo of the pathobiologic vascular remodeling in the retina and cornea.
登录
查看更多内容
DOI：
10.1098/rspb.1985.0021
发表时间：
1985-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DRAGER, UC
通讯作者：
DRAGER, UC
影响因子：
2.7
作者：
Halfter, W;Dong, S;Cole, GJ
通讯作者：
Cole, GJ
影响因子：
16.2
作者：
Deiner, MS;Kennedy, TE;Sretavan, DW
通讯作者：
Sretavan, DW
影响因子：
64.5
作者：
KeinoMasu, K;Masu, M;TessierLavigne, M
通讯作者：
TessierLavigne, M
影响因子：
4.8
作者：
Hurskainen, M;Eklund, L;Pihlajaniemi, T
通讯作者：
Pihlajaniemi, T