PMID- 18241851 OWN - NLM STAT- MEDLINE DCOM- 20080327 LR - 20211020 IS - 1095-564X (Electronic) IS - 0012-1606 (Print) IS - 0012-1606 (Linking) VI - 315 IP - 2 DP - 2008 Mar 15 TI - Drosophila growth and development in the absence of dMyc and dMnt. PG - 303-16 LID - 10.1016/j.ydbio.2007.12.026 [doi] AB - Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt. FAU - Pierce, Sarah B AU - Pierce SB AD - Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, POB 19024, Seattle, WA 98109-1024, USA. FAU - Yost, Cynthia AU - Yost C FAU - Anderson, Sarah A R AU - Anderson SA FAU - Flynn, Erin M AU - Flynn EM FAU - Delrow, Jeffrey AU - Delrow J FAU - Eisenman, Robert N AU - Eisenman RN LA - eng GR - R01 CA057138/CA/NCI NIH HHS/United States GR - R37 CA057138/CA/NCI NIH HHS/United States GR - R37 CA057138-16/CA/NCI NIH HHS/United States GR - R37CA57138/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20071227 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (DNA Primers) RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Myc protein, Drosophila) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Base Sequence MH - Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics/physiology MH - DNA Primers/genetics MH - DNA-Binding Proteins/deficiency/*genetics/physiology MH - Drosophila/*genetics/*growth & development/physiology MH - Drosophila Proteins/deficiency/*genetics/physiology MH - Female MH - Gene Deletion MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental MH - *Genes, Insect MH - Larva/growth & development MH - Male MH - Metamorphosis, Biological MH - *Mutation MH - Phenotype MH - Repressor Proteins/*genetics/physiology MH - Signal Transduction MH - Transcription Factors/deficiency/*genetics/physiology MH - Wings, Animal/growth & development PMC - PMC2322934 MID - NIHMS43178 EDAT- 2008/02/05 09:00 MHDA- 2008/03/28 09:00 PMCR- 2009/03/15 CRDT- 2008/02/05 09:00 PHST- 2007/10/08 00:00 [received] PHST- 2007/12/03 00:00 [revised] PHST- 2007/12/11 00:00 [accepted] PHST- 2008/02/05 09:00 [pubmed] PHST- 2008/03/28 09:00 [medline] PHST- 2008/02/05 09:00 [entrez] PHST- 2009/03/15 00:00 [pmc-release] AID - S0012-1606(07)01597-7 [pii] AID - 10.1016/j.ydbio.2007.12.026 [doi] PST - ppublish SO - Dev Biol. 2008 Mar 15;315(2):303-16. doi: 10.1016/j.ydbio.2007.12.026. Epub 2007 Dec 27.