Cell autonomy of HIF effects in Drosophila:: Tracheal cells sense hypoxia and induce terminal branch sprouting
Cell autonomy of HIF effects in Drosophila:: Tracheal cells sense hypoxia and induce terminal branch sprouting
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DOI：
10.1016/j.devcel.2008.01.020
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发表时间：
2008-04-01
影响因子：
11.8
通讯作者：
Wappner, Pablo
中科院分区：
文献类型：
--
作者：
Centanin, Lazaro;Dekanty, Andres;Wappner, Pablo
果蝇的气管末端分支是可塑的，有能力向缺氧区域长出突起，这一过程类似于哺乳动物的血管生成。这种反应涉及缺氧组织中FGF/Branchless的上调，其结合气管细胞上的其受体Breathless。在这里，我们表明，额外的发芽取决于缺氧诱导因子（HIF）-α同系物西玛和HIF-脯氨酰羟化酶Escheroga，作为氧传感器。在轻度缺氧时，司马积聚在气管细胞中，在那里它诱导呼吸困难，这种诱导足以引起气管额外发芽。在非气管细胞中，Sima有助于无分支诱导，而Sima的过表达不能吸引末端分支生长，这表明HIF-独立成分也是完全诱导配体所必需的。我们提出，自主反应缺氧发生在气管细胞增强气管的敏感性，增加无分支水平，这种机制是一个重要的步骤，缺氧依赖性气管发芽。
Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections toward oxygen-starved areas, in a process analogous to mammalian angiogenesis. This response involves the upregulation of FGF/Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells. Here, we show that extra sprouting depends on the Hypoxia-Inducible Factor (HIF)-alpha homolog Sima and on the HIF-prolyl hydroxylase Fatiga that operates as an oxygen sensor. In mild hypoxia, Sima accumulates in tracheal cells, where it induces breathless, and this induction is sufficient to provoke tracheal extra sprouting. In nontracheal cells, Sima contributes to branchless induction, whereas overexpression of Sima fails to attract terminal branch outgrowth, suggesting that HIF-independent components are also required for full induction of the ligand. We propose that the autonomous response to hypoxia that occurs in tracheal cells enhances tracheal sensitivity to increasing Branchless levels, and that this mechanism is a cardinal step in hypoxia-dependent tracheal sprouting.