An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control.
BACKGROUND
Size regulation is fundamental in developing multicellular organisms and occurs through the control of cell number and cell size. Studies in Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K.


RESULTS
We demonstrate that varying the activity of the Drosophila insulin receptor homolog (DInr) during development regulates organ size by changing cell size and cell number in a cell-autonomous manner. An amino acid substitution at the corresponding position in the kinase domain of the human and Drosophila insulin receptors causes severe growth retardation. Furthermore, we show that the Drosophila genome contains seven insulin-like genes that are expressed in a highly tissue- and stage-specific pattern. Overexpression of one of these insulin-like genes alters growth control in a DInr-dependent manner.


CONCLUSIONS
This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size.
Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
W
W
Brogiolo
H
H
Stocker
T
T
Ikeya
F
F
Rintelen
R
R
Fernandez
E
E
Hafen
D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D002452:Cell Count; D002455:Cell Division; D048429:Cell Size; D017124:Conserved Sequence / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D019143:Evolution, Molecular; D015870:Gene Expression; D005786:Gene Expression Regulation; D017344:Genes, Insect; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000596:Amino Acids; D019476:Insect Proteins; D007328:Insulin; D010455:Peptides; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin