Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9240-5. doi: 10.1073/pnas.0913748107. Epub 2010 May 3.
The kidney develops through reciprocal interactions between two precursor tissues: the metanephric mesenchyme and the ureteric bud. We previously demonstrated that the zinc finger protein Sall1 is essential for ureteric bud attraction toward the mesenchyme. Here, we show that Kif26b, a kinesin family gene, is a downstream target of Sall1 and that disruption of this gene causes kidney agenesis because of impaired ureteric bud attraction. In the Kif26b-null metanephros, compact adhesion between mesenchymal cells adjacent to the ureteric buds and the polarized distribution of integrin alpha8 were impaired, resulting in failed maintenance of Gdnf, a critical ureteric bud attractant. Overexpression of Kif26b in vitro caused increased cell adhesion through interactions with nonmuscle myosin. Thus, Kif26b is essential for kidney development because it regulates the adhesion of mesenchymal cells in contact with ureteric buds.
后肾间充质和输尿管芽。我们之前证明锌指蛋白 Sall1 对于输尿管芽向间充质的吸引是必需的。在这里,我们表明驱动蛋白家族基因 Kif26b 是 Sall1 的下游靶标,并且该基因的破坏会导致肾脏发育不全,因为输尿管芽的吸引力受损。在 Kif26b 缺失的后肾中,相邻于输尿管芽的间充质细胞之间的紧密黏附以及整合素 alpha8 的极化分布受到损害,导致关键的输尿管芽吸引物 Gdnf 的维持失败。在体外过表达 Kif26b 通过与非肌肉肌球蛋白的相互作用引起细胞黏附增加。因此,Kif26b 对于肾脏发育是必需的,因为它调节与输尿管芽接触的间充质细胞的黏附。