Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, USA.
Adv Exp Med Biol. 2012;727:99-113. doi: 10.1007/978-1-4614-0899-4_8.
The kidney is the body's filter, responsible for the removal of metabolic waste and the excretion or reabsorption of electrolytes to control blood composition and pH balance. The functional unit of this filter is the nephron, whose segmented architecture has been largely conserved in form and function throughout eukaryotic evolution. Not surprisingly, the core developmental pathways that regulate the formation of the nephron have also been conserved. In particular, the Notch signaling pathway functions in both primitive and advanced nephrons to pattern domains required for the kidney's diverse functions. In this chapter, we will discuss the role that Notch plays in directing cell fate decisions during embryonic development of the pronephros and metanephros. We will go on to discuss the later role of Notch signaling as a cyst-suppressor and the consequences of aberrant or absent Notch activity in disease and cancer. The work discussed here highlights the fundamental importance of Notch during development and homeostasis of the kidney and underlies the need for mechanistic understanding of its role towards the treatment of human disease.
肾脏是人体的过滤器，负责清除代谢废物和排泄或重吸收电解质，以控制血液成分和 pH 值平衡。这个过滤器的功能单位是肾单位，其分段结构在整个真核生物进化过程中在形式和功能上都得到了很大的保留。毫不奇怪，调节肾单位形成的核心发育途径也得到了保留。特别是，Notch 信号通路在原始和高级肾单位中都发挥作用，以形成肾脏多种功能所需的结构域。在这一章中，我们将讨论 Notch 在指导胚胎发育过程中肾前体和后肾的细胞命运决定中的作用。我们将继续讨论 Notch 信号在作为囊肿抑制剂的后期作用，以及 Notch 活性异常或缺失在疾病和癌症中的后果。这里讨论的工作强调了 Notch 在肾脏发育和稳态中的基本重要性，并为理解其在治疗人类疾病方面的作用的机制提供了基础。
