Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4640-5. doi: 10.1073/pnas.1213971110. Epub 2013 Mar 4.
Embryonic nephron progenitor cells are segregated in molecularly distinct compartments of unknown function. Our study reveals an integral role for bone morphogenetic protein-SMAD in promoting transition of progenitors from the primitive Cbp/p300-interacting transactivator 1 expressing (CITED1+) compartment to the uniquely sine oculis-related homeobox 2 expressing (SIX2-only) compartment where they become inducible by wingless-type mouse mammary tumor virus integration site family member (WNT)/β-catenin signaling. Significantly, CITED1(+) cells are refractory to WNT/β-catenin induction. We propose a model in which the primitive CITED1(+) compartment is refractory to induction by WNT9b/β-catenin, ensuring maintenance of undifferentiated progenitor cells for future nephrogenesis. Bone morphogenetic protein 7-SMAD is then required for transition to a distinct compartment in which cells become inducible by WNT9b/β-catenin, allowing them to progress toward epithelialization.
胚胎肾祖细胞被分隔在功能未知的分子上不同的隔室中。我们的研究揭示了骨形态发生蛋白-SMAD 在促进祖细胞从原始 Cbp/p300 相互作用的转录激活因子 1 表达（CITED1+）隔室向独特的 sine oculis 相关同源盒 2 表达（SIX2-only）隔室过渡中的重要作用，在后者中，它们可以被 Wnt/β-连环蛋白信号诱导。重要的是，CITED1(+)细胞对 WNT/β-连环蛋白诱导具有抗性。我们提出了一个模型，其中原始的 CITED1(+)隔室对 WNT9b/β-连环蛋白的诱导具有抗性，从而确保未分化祖细胞的维持，以备未来的肾发生。然后，骨形态发生蛋白 7-SMAD 对于向一个可以通过 WNT9b/β-连环蛋白诱导的不同隔室的转变是必需的，从而允许细胞向上皮化方向发展。
