昆虫体内的循环系统一般不参与氧气运输，各组织和器官所需的氧气直接由气管系统供应。与哺乳动物的血管生成过程相似，昆虫气管的末端也能够产生分枝并侵入缺氧组织内。
以往研究表明，果蝇体内处于缺氧状态的细胞会产生Bnl，这是成纤维细胞生长因子的同源体，其受体Btl位于气管细胞表面，Bnl能够诱导气管细胞分枝伸入缺氧组织内，这就是气管生成的“Bnl中心模式”。
Centanin等人的研究工作进一步揭示了气管末端分枝的形成机制，果蝇气管末端的细胞本身对缺氧环境也非常敏感，缺氧条件下，对氧含量敏感的脯氨酰羟化酶Fatiga能够增加缺氧诱导因子Similar（Sima）的浓度，Sima是人类缺氧诱导因子（HIFs）的同源分子，能够诱导Btl的表达，增加气管末端细胞中Btl的浓度，促使细胞产生分枝。而在非气管细胞内，Sima能够诱导Bnl的表达，但也可能有其它一些因子参与该过程。
研究人员指出，气管末端细胞在缺氧条件下通过自主反应，增加其表面受体Btl的浓度，能够使其对组织Bnl水平增加更加敏感，是缺氧诱导气管分枝的重要步骤。此即“搜索模式”，和此前的“Bnl中心模式”一起更好解释了气管分枝发生的机制，这一理论对哺乳动物的血管发生机制也有一定的启示。
该研究以封面论文形式发表于4月15日的《发育细胞》（Developmental Cell）上。（科学网 穆宏平/编译）
生物谷推荐原始出处：
（Developmental Cell），Vol 14, 547-558, 15 April 2008，Lázaro Centanin, Pablo Wappner
Cell Autonomy of HIF Effects in Drosophila: Tracheal Cells Sense Hypoxia and Induce Terminal Branch Sprouting
Lázaro Centanin,1,4 Andrés Dekanty,1 Nuria Romero,1 Maximiliano Irisarri,1 Thomas A. Gorr,2,3 and Pablo Wappner1,3,
1 Instituto Leloir and FBMC, FCEyN-Universidad de Buenos Aires, CONICET, Patricias Argentinas 435, Buenos Aires 1405, Argentina
2 Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Wintherthurerstrasse 260, CH-8057 Zurich, Switzerland
Summary
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)-α 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.
