Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching.
During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives--rather than responds to--metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture.
Gut Signalling and Metabolism Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Gerit A
GA
Linneweber
Gut Signalling and Metabolism Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Jake
J
Jacobson
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Karl Emanuel
KE
Busch
Gut Signalling and Metabolism Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Bruno
B
Hudry
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Christo P
CP
Christov
Gut Signalling and Metabolism Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Dirk
D
Dormann
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Michaela
M
Yuan
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Tomoki
T
Otani
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Elisabeth
E
Knust
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Mario
M
de Bono
Gut Signalling and Metabolism Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address: i.miguel-aliaga@imperial.ac.uk.
Irene
I
Miguel-Aliaga
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004064:Digestive System / Q000098:blood supply; D004331:Drosophila melanogaster / Q000502:physiology*; D006801:Humans; D023421:Models, Animal; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D010100:Oxygen; D002118:Calcium