Editors' ChoiceDevelopmental Biology

Synchronizing Developmental Timing with Growth

Sci. Signal.  08 May 2012:
Vol. 5, Issue 223, pp. ec129
DOI: 10.1126/scisignal.2003189

Conspecific individuals exhibit similar body size and proportions because they can adjust their developmental timing to compensate for variations in both internal and external conditions during development. In the fruit fly Drosophila melanogaster, the onset of metamorphosis (pupariation) at the end of the third larval stage may be delayed by unfavorable environmental conditions or by tissue damage until the animal has reached a target size. Two groups have identified Dilp8 (Drosophila insulin-like peptide 8) as a secreted signal that coordinates tissue growth with developmental timing in the fruit fly. Garelli et al. noted that dilp8 was increased in expression in eye disc tumors and demonstrated that a loss-of-function mutation in dilp8 rescued the developmental delay caused by the presence of eye disc tumors or by genotoxin-induced tissue damage. These loss-of-function dilp8 mutants exhibited greater variability in the timing of pupariation and in body size and showed increased bilateral asymmetry compared with wild-type animals. Colombani et al. found that reducing the expression of dilp8 by RNA interference rescued the delay in pupariation exhibited by animals in which imaginal disc growth was delayed by genetic manipulation, but genetic deletion of dilp8 in otherwise normal animals only mildly accelerated pupariation. Both groups demonstrated that dilp8 overexpression delayed pupariation and reduced production of the metamorphosis-inducing steroid hormone ecdysone. Dilp8 was secreted from disc cells in vivo, and Colombani and colleagues demonstrated that secretion was required for Dilp8 function. These findings suggest that Dilp8 is an endocrine signal that regulates developmental timing when tissue growth is delayed as part of a feedback mechanism that enables an organism to compensate for the extra time required to repair or regenerate damaged tissues.

A. Garelli, A. M. Gontijo, V. Miguela, E. Caparros, M. Dominguez, Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579–582 (2012). [Abstract] [Full Text]

J. Colombani, D. S. Andersen, P. Léopold, Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing. Science 336, 582–585 (2012). [Abstract] [Full Text]