Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis.
In the developing kidney, activation of the rearrangement during transfection tyrosine kinase by glial cell line-derived neurotrophic factor (GDNF) is required for normal branching of the ureteric bud epithelium [corrected]. By differential display analysis we identified a novel GDNF-inducible gene (named GZF1) with a BTB/POZ (broad complex, tramtrack, and bric-a-brac)/(poxvirus and zinc finger) domain and 10 tandemly repeated zinc finger motifs. The up-regulation of the GZF1 gene showed two peaks at 1 h and 24-48 h after GDNF stimulation by Northern blotting. The late induction was also found at protein levels by Western blotting with anti-GZF1 antibody. As observed for other proteins with the BTB/POZ domain, the GZF1 protein had strong transcriptional repressive activity. Intriguingly, its expression was detected at high levels in branching ureteric buds and collecting ducts of mouse metanephric kidney in which RET was also expressed. Antisense phosphorothioated oligodeoxynucleotides of the GZF1 gene markedly impaired the ureteric bud branching in the metanephric organ culture, suggesting that the induction of GZF1 expression via the GDNF/RET signaling system is required for renal branching morphogenesis.
Fukuda
Naoyuki
N
Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Ichihara
Masatoshi
M
Morinaga
Takatoshi
T
Kawai
Kumi
K
Hayashi
Hironori
H
Murakumo
Yoshiki
Y
Matsuo
Seiichi
S
Takahashi
Masahide
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000196:embryology; D020869:Gene Expression Profiling; D015723:Gene Library; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D009924:Organ Culture Techniques; D020161:Physical Chromosome Mapping; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D014513:Ureter / Q000378:metabolism
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C495039:GDNF protein, human; C480233:GZF1 protein, human; C480234:GZF1 protein, mouse; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051741:Kruppel-Like Transcription Factors; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D008156:Luciferases