Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division.
Mutations in the Drosophila trol gene cause cell cycle arrest of neuroblasts in the larval brain. Here, we show that trol encodes the Drosophila homolog of Perlecan and regulates neuroblast division by modulating both FGF and Hh signaling. Addition of human FGF-2 to trol mutant brains in culture rescues the trol proliferation phenotype, while addition of a MAPK inhibitor causes cell cycle arrest of the regulated neuroblasts in wildtype brains. Like FGF, Hh activates stem cell division in the larval brain in a Trol-dependent fashion. Coimmunoprecipitation studies are consistent with interactions between Trol and Hh and between mammalian Perlecan and Shh that are not competed with heparin sulfate. Finally, analyses of mutations in trol, hh, and ttv suggest that Trol affects Hh movement. These results indicate that Trol can mediate signaling through both of the FGF and Hedgehog pathways to control the onset of stem cell proliferation in the developing nervous system.
Park
Youngji
Y
Department of Biochemistry and Biophysics, Texas A&M University, TAMU 2128, College Station, TX 77843-2128, USA.
Rangel
Carolina
C
Reynolds
M Megan
MM
Caldwell
M Craig
MC
Johns
Misty
M
Nayak
Mamatha
M
Welsh
C Jane R
CJ
McDermott
Sean
S
Datta
Sumana
S
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C071927:perlecan; C077245:hh protein, Drosophila; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one