Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms.
In newly hatched Drosophila larvae, quiescent cells reenter the cell cycle in response to dietary amino acids. To understand this process, we varied larval nutrition and monitored effects on cell cycle initiation and maintenance in the mitotic neuroblasts and imaginal disc cells, as well as the endoreplicating cells in other larval tissues. After cell cycle activation, mitotic and endoreplicating cells respond differently to the withdrawal of nutrition: mitotic cells continue to proliferate in a nutrition-independent manner, while most endoreplicating cells reenter a quiescent state. We also show that ectopic expression of Drosophila Cyclin E or the E2F transcription factor can drive quiescent endoreplicating cells, but not quiescent imaginal neuroblasts, into S-phase. Conversely, we demonstrate that quiescent imaginal neuroblasts, but not quiescent endoreplicating cells, can be induced to enter the cell cycle when co-cultured with larval fat body in vitro. These results demonstrate a fundamental difference in the control of cell cycle activation and maintenance in these two cell types, and imply the existence of a novel mitogen generated by the larval fat body in response to nutrition.
Britton
J S
JS
Molecular and Cellular Biology Program and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
Edgar
B A
BA
D000596:Amino Acids / Q000494:pharmacology*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D046508:Culture Techniques; D004261:DNA Replication / Q000187:drug effects; D004330:Drosophila / Q000166:cytology* / Q000187:drug effects; D029721:Drosophila Proteins; D004777:Environment; D005216:Fat Body / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D019476:Insect Proteins / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology; D015398:Signal Transduction; D013234:Stem Cells
D000596:Amino Acids; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D019476:Insect Proteins; D008934:Mitogens; C082255:ana protein, Drosophila