Identification of a Novel Glial Cell Line-derived Neurotrophic Factor-inducible Gene Required for Renal Branching Morphogenesis

Naoyuki Fukuda, Masatoshi Ichihara, Takatoshi Morinaga, Kumi Kawai, Hironori Hayashi, Yoshiki Murakumo, Seiichi Matsuo, Masahide Takahashi

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

In the developing kidney, activation of the rearrangement during transfection by glial cell line-derived neurotrophic factor (GDNF) is required for normal branching of the ureteric bud epithelium. 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.

Original languageEnglish
Pages (from-to)50386-50392
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number50
DOIs
Publication statusPublished - 12-12-2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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