Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis
Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis
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DOI：
10.1074/jbc.m309629200
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发表时间：
2003-12-12
影响因子：
4.8
通讯作者：
Takahashi, M
中科院分区：
文献类型：
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作者：
Fukuda, N;Ichihara, M;Takahashi, M
在发育中的肾脏中，胶质细胞系衍生神经营养因子(GDNF)在转导过程中激活重排是输尿管芽上皮正常分支所必需的。通过差异显示分析，我们发现了一个新的GDNF诱导基因(命名为GZF1)，它含有一个BTB/POZ结构域(BTB/POZ)/(痘病毒和锌指)结构域和10个重复的锌指基序。Northern印迹显示GZF1基因在刺激后1h和24~48h出现两个上调高峰。用抗GZF1抗体进行Western blotting，在蛋白水平上也发现晚期诱导。与其他含有BTB/POZ结构域的蛋白一样，GZF1蛋白具有很强的转录抑制活性。有趣的是，它在小鼠后肾的分支输尿管芽和集合管中检测到高水平的表达，其中RET也表达。GZF1基因的反义硫代寡核苷酸显著损伤后肾器官培养中的输尿管芽分枝，提示GZF1的表达是通过GDNF/RET信号系统诱导的。
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.