Polyamines are involved in murine kidney development controlling expression of c-ret, E-cadherin, and Pax2/8 genes

Autor: Seppo Vainio, Antti Pajunen, Antti Railo, Ildikó Loikkanen, Yanfeng Lin
Rok vydání: 2005
Předmět:
Cancer Research
Eflornithine
Glial Cell Line-Derived Neurotrophic Factor Receptors
Transcription
Genetic
Organogenesis
Morphogenesis
Kidney development
Biology
Kidney
Ornithine Decarboxylase
Ornithine decarboxylase
Cell Line
chemistry.chemical_compound
Mice
PAX8 Transcription Factor
Genes
Reporter
Proto-Oncogene Proteins
Polyamines
Animals
Paired Box Transcription Factors
Enzyme Inhibitors
Enhancer
Promoter Regions
Genetic
Molecular Biology
urogenital system
Cadherin
HEK 293 cells
PAX2 Transcription Factor
Proto-Oncogene Proteins c-ret
Gene Expression Regulation
Developmental
Nuclear Proteins
Receptor Protein-Tyrosine Kinases
Cell Biology
Ornithine Decarboxylase Inhibitors
Cadherins
Molecular biology
DNA-Binding Proteins
chemistry
Ureteric bud
Trans-Activators
Polyamine
Developmental Biology
Transcription Factors
Zdroj: Differentiation; research in biological diversity. 73(6)
ISSN: 0301-4681
Popis: Polyamines play an important role in cell growth and differentiation. We studied changes in morphogenesis and the expression of the developmental control genes in the embryonic mouse kidney in response to polyamine depletion, using a kidney organ culture approach and reducing the polyamine pools with α-difluoromethylornithine (DFMO), an irreversible suicide inhibitor of ornithine decarboxylase (ODC). We found that inhibition of ODC results in a systematic kidney organogenesis phenotype, in that the DFMO-treated kidney specimens were of smaller size, had less epithelial ureteric bud branches, and their mesenchymal-derived tubule formation was retarded. These dysmorphologies were shown to be associated with changes in cell proliferation. Whole-mount in situ experiments revealed that inhibition of ODC causes increases in epithelial c-ret and E-cadherin and a decrease in mesenchymal Pax-8 expression, whereas levels of epithelial Wnt-11, mesenchymal GDNF, FoxD1, and Pax-2 transcripts remain unchanged. We studied regulation of the Pax-2 gene by analyzing a mouse line in which lacZ was driven by an 8.5 kb Pax-2 enhancer in the epithelial ureteric bud, and found that Pax-2 expression, as indicated by lacZ expression, increased after DFMO treatment. Transient transfection experiments in HEK 293 cells with the minimal Pax-2 promoter showed enhanced transcription upon reduction of the polyamine pools. We propose that ODC and polyamines have an important role in kidney organogenesis, being involved in the regulation of the expression of genes implicated in epithelial–mesenchymal tissue interactions.
Databáze: OpenAIRE
Externí odkaz: