Endocrine-Genetic Network Regulation of Drosophila Life History
Friday Seminar by Thomas Flatt.
Trade-offs between reproduction and lifespan are ubiquitous, but little is known about their underlying mechanisms. Since endocrine mechanisms ensure the global coordination of physiological and developmental processes in response to environmental cues, from the cellular to the organismal level, hormones might play a major role in pleiotropically regulating reproduction and lifespan. For example, ablation of germline precursor cells in the nematode worm C. elegans extends lifespan by activating DAF-16, a forkhead transcription factor (FOXO) repressed by insulin/insulin growth factor signaling (IIS). Signals from the gonad might thus regulate whole-organism aging by modulating IIS. To date, the details of systemic regulation of aging by the germ line are not understood, and it is unknown whether such effects are evolutionarily conserved. In the first part of my talk, I report that eliminating germ cells (GCs) in the fruit fly, D. melanogaster increases lifespan and modulates insulin signaling. Long-lived germline-less flies show increased production of Drosophila insulin-like peptides (dilps) by median neurosecretory cells, but simultaneously these animals exhibit insulin signaling impedance, as indicated by upregulation of the Drosophila FOXO (dFOXO) target genes 4E-BP and l(2)efl and the insulin-binding protein IMP-L2, a DILP antagonist and inhibitor of IIS. These results suggest that signals from the germ line regulate lifespan by modulating insulin sensitivity downstream of dilp production. In the second part of my talk, I report that the trade-off between reproduction and lifespan is, at least partly, regulated by secondary lipophilic hormones downstream of IIS, the reproductive hormones juvenile hormone (JH) and 20-hydroxy-ecdysone (20E). JH and 20E both shorten lifespan at the expense of reproduction, and JH also functions as major immuno-suppressor. The rapid progress made by molecular biologists in identifying candidate mechanisms affecting life history traits enables evolutionary biologists to determine whether there is standing genetic variance for such mechanisms in natural populations and whether they are under selection.Other information
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