Cited1 and cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis

Cited1 and cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis
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DOI:
10.1002/dvdy.21242
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发表时间:
2007-08-01
影响因子:
2.5
通讯作者:
de Caestecker, Mark
de Caestecker, Mark
中科院分区:
生物学3区
文献类型:
--
作者:
Boyle, Scott;Shioda, Toshi;de Caestecker, Mark

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哺乳动物早期肾脏发育的特征是输尿管芽和后肾间充质之间的相互组织作用。对这种相互作用的协调反应主要在转录水平上调节。在这里,我们调查的表达和功能的Cited1,转录辅因子,我们以前有牵连的肾脏发育。我们发现,Cited1是在后肾间充质中表达的输尿管芽入侵后,其表达仅限于帽间充质,这些细胞聚集最紧密的输尿管芽的尖端周围,并引起成人肾的肾上皮。Cited1在上皮转化的初始阶段下调,并且在此祖细胞阶段后不表达。尽管其独特的表达模式,Cited1的缺失不会破坏肾脏发育。我们假设这一发现是由于该基因家族其他成员的功能冗余。Cited2的表达模式与Cited1的表达模式重叠,但其缺失,单独或与Cited1组合,不会破坏后肾间充质的上皮分化。从这些研究中,我们得出结论,Cited1和2在肾脏发育过程中动态表达,但不是肾发生所必需的。
Early kidney development in mammals is characterized by reciprocal tissue interaction between the ureteric bud and the metanephric mesenchyme. The coordinated response to this interaction is regulated largely at the transcriptional level. Here, we investigate the expression and function of Cited1, a transcriptional cofactor that we have previously implicated in kidney development. We show that Cited1 is expressed in the metanephric mesenchyme after invasion of the ureteric bud and that its expression is limited to the cap mesenchyme, those cells that aggregate most tightly around the tip of the ureteric bud and give rise to nephronic epithelium of the adult kidney. Cited1 is down-regulated during the initial stages of epithelial conversion and is not expressed past this progenitor stage. Despite its unique expression pattern, deletion of Cited1 does not disrupt kidney development. We hypothesized that this finding was due to functional redundancy with other members of this gene family. The expression pattern of Cited2 overlaps that of Cited1, but its deletion, either alone or in combination with Cited1, does not disrupt epithelial differentiation of the metanephric mesenchyme. From these studies, we conclude that Cited1 and 2 are dynamically expressed during kidney development, but are not required for nephrogenesis.