Department of Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
Pediatr Nephrol. 2011 Sep;26(9):1491-7. doi: 10.1007/s00467-011-1819-8. Epub 2011 Mar 4.
Bone morphogenic proteins (BMPs) play diverse roles in embryonic kidney development, regulating essential aspects of both ureteric bud and nephron development. In this review, we provide an overview of reported expression patterns and functions of BMP signaling components within the nephrogenic zone or nephron progenitor niche of the developing kidney. Reported in situ hybridization results are relatively challenging to interpret and sometimes conflicting. Comparing these with high-resolution microarray gene expression data available in Gudmap, we propose a consensus gene expression pattern indicating that essential components of both the Smad-mediated pathway and the Smad-independent MAPK pathways are expressed in the nephron progenitor cell compartment and may be activated by BMPs, but that cortical interstitium may only be able to respond to BMPs through mitogen activated protein kinase (MAPK) signaling. Localization of phosphorylated Smad transcription factors and studies of a BMP reporter mouse strain however indicate limited transcriptional responsiveness to Smad-mediated signaling in cap mesenchyme. An overview of genetic inactivation, organ culture, and primary cell studies indicates that BMP signaling may elicit two important biological outcomes in the nephrogenic zone: survival of the cap mesenchyme, and the physical segregation of interstitial and progenitor cell compartments. Ongoing studies using a novel primary cell system that establishes the nephrogenic zone ex vivo are pursuing the concept that the balance between Smad-mediated and Smad-independent responses to BMP ligand may underlie these distinct outcomes.
骨形态发生蛋白（BMPs）在胚胎肾发育中发挥多种作用，调节输尿管芽和肾单位发育的重要方面。在这篇综述中，我们概述了在发育肾脏的肾发生区或肾单位祖细胞龛内报道的 BMP 信号成分的表达模式和功能。报道的原位杂交结果相对难以解释，有时甚至相互矛盾。将这些结果与 Gudmap 中提供的高分辨率微阵列基因表达数据进行比较，我们提出了一个共识基因表达模式，表明 Smad 介导途径和 Smad 非依赖性 MAPK 途径的基本组成部分都在肾单位祖细胞区室中表达，并且可能被 BMP 激活，但皮质间质可能只能通过丝裂原激活的蛋白激酶 (MAPK) 信号转导对 BMP 作出反应。磷酸化 Smad 转录因子的定位和 BMP 报告鼠系的研究表明，帽间充质对 Smad 介导的信号转导的转录反应性有限。遗传失活、器官培养和原代细胞研究的概述表明，BMP 信号在肾发生区可能产生两个重要的生物学结果：帽间充质的存活和间质和祖细胞区室的物理隔离。正在使用一种新颖的原代细胞系统进行的研究，该系统在体外建立肾发生区，正在探索 BMP 配体对 Smad 介导和 Smad 非依赖性反应的平衡可能是这些不同结果的基础的概念。
