Abstract
Organisms modulate their growth according to nutrient availability. Although individual cells in a multicellular animal may respond directly to nutrient levels, growth of the entire organism needs to be coordinated. Here, we provide evidence that in Drosophila, coordination of organismal growth originates from the fat body, an insect organ that retains endocrine and storage functions of the vertebrate liver. In a genetic screen for growth modifiers, we identified slimfast, a gene that encodes an amino acid transporter. Remarkably, downregulation of slimfast specifically within the fat body causes a global growth defect similar to that seen in Drosophila raised under poor nutritional conditions. This involves TSC/TOR signaling in the fat body, and a remote inhibition of organismal growth via local repression of PI3-kinase signaling in peripheral tissues. Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism.
| Original language | English |
|---|---|
| Journal | Cell |
| Volume | 114 |
| Issue number | 6 |
| Pages (from-to) | 739-49 |
| Number of pages | 11 |
| ISSN | 0092-8674 |
| Publication status | Published - 19 Sept 2003 |
| Externally published | Yes |
Keywords
- Amino Acid Transport Systems/deficiency
- Amino Acids/deficiency
- Animals
- Down-Regulation/physiology
- Drosophila Proteins/deficiency
- Drosophila melanogaster/cytology
- Fat Body/metabolism
- Feedback, Physiological/genetics
- Food Deprivation/physiology
- Gene Expression Regulation, Developmental/genetics
- Juvenile Hormones/deficiency
- Nutritional Physiological Phenomena/physiology
- Phosphatidylinositol 3-Kinases/metabolism
- Receptor Protein-Tyrosine Kinases/metabolism
- Signal Transduction/physiology