Boyle Scott, Shioda Toshi, Perantoni Alan O, de Caestecker Mark
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
Dev Dyn. 2007 Aug;236(8):2321-30. doi: 10.1002/dvdy.21242.
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.
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在很大程度上是在转录水平上调控的。在这里,我们研究了Cited1的表达和功能,Cited1是一种转录辅因子,我们之前认为它与肾脏发育有关。我们发现,在输尿管芽侵入后,Cited1在后肾间充质中表达,并且其表达仅限于帽状间充质,即那些最紧密聚集在输尿管芽尖端周围并产生成年肾脏肾单位上皮的细胞。在上皮转化的初始阶段,Cited1表达下调,并且在这个祖细胞阶段之后不再表达。尽管其表达模式独特,但Cited1的缺失并不破坏肾脏发育。我们推测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重叠,但其单独缺失或与Cited1联合缺失均不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Cited2在肾脏发育过程中动态表达,但对肾发生并非必需。