Angiogenis like response of the Drosophila tracheal system.

WAPPNER, P.

Edinburgo, Escocia

Congreso; 16th International Society of Developmental Biologists Congress.; 2009

International Society of Developmental Biologists

Angiogenic-like response to hypoxia of the Drosophila tracheal system 1Lázaro Centanin, 1Andrés Dekanty, 1Nuria M. Romero,  2Thomas A. Gorr and 1Pablo Wappner 1Instituto Leloir, Patricias Argentinas 435, Buenos Aires (1405), ARGENTINA 2Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Wintherthurerstrasse 260, CH-8057 Zurich, Switzerland. Drosophila tracheal terminal branches are plastic and have the capacity to sprout-out projections towards oxygen-starved areas, in a process analogous to mammalian angiogenesis. It was previously shown that this sprouting response involves the upregulation of the FGF homolog Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells, thereby attracting the outgrowth of terminal cells. We have found that tracheal extra-sprouting depends on the Hypoxia Inducible Factor alpha-subunit Sima, as well as on the HIF prolyl hydroxylase Fatiga that operates as an oxygen sensor. In mild hypoxia, Sima accumulates mainly in tracheal terminal cells, where it promotes transcriptional upregulation of the receptor breathless. Strikingly, this induction is sufficient to provoke extra-sprouting of tracheal terminal branches. In non-tracheal cells, Sima contributes to induction of the ligand branchless, whilst over-expression of Sima fails on itself 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 levels of the ligand Branchless, and that this mechanism is a cardinal step in hypoxia-dependent tracheal sprouting.