title: The tumor suppressor, vitamin D3 up-regulated protein 1 (VDUP1), functions downstream of REPO during Drosophila gliogenesis.
abstract: The tumor suppressor, vitamin D(3) up-regulated protein 1 (VDUP1), regulates cell cycle progression by suppressing AP-1-dependent transcription. Loss of VDUP1 activity is associated with tumorigenesis but little is known about VDUP1 regulatory controls or developmental roles. Here we show that the Drosophila homolog of human VDUP1 (dVDUP1) is expressed throughout the nervous system at all stages of development, the first in vivo analysis of VDUP1 expression patterns in the brain. During neurogenesis dVDUP1 expression is transiently down-regulated coincident with neuroblast delamination. Subsequent to expression of the neuronal marker elav, dVDUP1 is up-regulated to varying degrees in developing neurons. In contrast, dVDUP1 expression is both robust and sustained during gliogenesis, and the cis-regulatory region of the dvdup1 gene contains consensus binding sites for the glial fate gene reversed polarity (repo). Expression of dVDUP1 in presumptive glia is lost in embryos deficient for the glial fate genes glial cells missing (gcm) and repo. Conversely, ectopic expression of gcm or repo was sufficient to induce dVDUP1 expression in the nervous system. Taken together, these data suggest a novel role for the dVDUP1 tumor suppressor during nervous system development as a regulatory target for REPO during gliogenesis.
authors.affiliation: Department of Pharmaceutical Sciences, Albany College of Pharmacy, O'Brien Building, Room 017C, 106 New Scotland Ave, Albany, NY 12208, USA.
authors.forename: Neil V
authors.initials: NV
authors.lastname: Mandalaywala
authors.forename: Solomon
authors.initials: S
authors.lastname: Chang
authors.forename: Randall G
authors.initials: RG
authors.lastname: Snyder
authors.forename: Mark C
authors.initials: MC
authors.lastname: Levendusky
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Voigt
authors.forename: Richard E
authors.initials: RE
authors.lastname: Dearborn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D002762:Cholecalciferol / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; C089972:repo protein, Drosophila; D002762:Cholecalciferol