肾发育
中文名称
通路描述
哺乳动物（如小鼠或人类）的肾单位包括肾小球，其中小分子从血液中过滤；近端小管和亨氏袢，其中小分子被选择性重吸收；厚升支、致密斑、远端小管、连接小管和收集管，这些管汇合流入输尿管。
肾发育的起始发生在输尿管芽的末端，输尿管芽的细胞与间肾中胚层的细胞相互作用。而不是原位分化，分析细胞迁移表明，间肾细胞被招募到正在发育的肾单位上皮元素中（Lindstrom et al. 2018）。在人类肾生成期间运行的转录组已被详细绘制（Lindstrom et al. 2021）。由输尿管芽分泌的 WNT9B 诱导肾祖细胞的一个亚群聚集并表达 WNT4，导致前管聚集进一步经历间质到上皮转换以形成肾囊泡（从小鼠胚胎推断，Park et al. 2007，综述 El-Dahr et al. 2008, Costantini and Kopan 2010, Desgrange and Cereghini 2015）。肾祖细胞的一个亚群表达 SIX2，并响应 WNT9B 而增殖，以维持肾祖细胞的再生种群。WNT9B 局部浓度（从小鼠胚胎推断，Ramalingam et al. 2018）或 SIX2 转录因子的存在（从小鼠胚胎推断，Karner et al. 2011）可能是反应差异的原因。
肾囊泡早期发生极化。远端区域包含一个基因调控网络，包含 LHX1、POU3F3（BRN1）、DLL1 和 JAG1。LHX1 对于近端 - 远端分化是必需的（从小鼠胚胎推断，Kobayashi et al. 2005），POU3F3 参与亨氏袢的延伸和远端小管的形成（从小鼠胚胎推断，Nakai et al. 2003）。肾囊泡的近端区域表达 WT1，直接抑制 PAX2，从而允许足细胞形成（从小鼠同源物推断，Ryan et al. 1995）。肾囊泡发育成逗号状体，其中 HNF1B 在远端区域激活 NOTCH 通路组件 DLL1、JAG1 和 LFNG（从小鼠胚胎推断，Heliot et al. 2013）。逗号状体随后发育成 S 形体，其中 HNF1B 激活 IRX1 和 IRX2 在中间区域（从小鼠胚胎推断，Heliot et al. 2013）。足细胞、近端小管、中间小管和远端小管随后分化。
肾发育的起始发生在输尿管芽的末端，输尿管芽的细胞与间肾中胚层的细胞相互作用。而不是原位分化，分析细胞迁移表明，间肾细胞被招募到正在发育的肾单位上皮元素中（Lindstrom et al. 2018）。在人类肾生成期间运行的转录组已被详细绘制（Lindstrom et al. 2021）。由输尿管芽分泌的 WNT9B 诱导肾祖细胞的一个亚群聚集并表达 WNT4，导致前管聚集进一步经历间质到上皮转换以形成肾囊泡（从小鼠胚胎推断，Park et al. 2007，综述 El-Dahr et al. 2008, Costantini and Kopan 2010, Desgrange and Cereghini 2015）。肾祖细胞的一个亚群表达 SIX2，并响应 WNT9B 而增殖，以维持肾祖细胞的再生种群。WNT9B 局部浓度（从小鼠胚胎推断，Ramalingam et al. 2018）或 SIX2 转录因子的存在（从小鼠胚胎推断，Karner et al. 2011）可能是反应差异的原因。
肾囊泡早期发生极化。远端区域包含一个基因调控网络，包含 LHX1、POU3F3（BRN1）、DLL1 和 JAG1。LHX1 对于近端 - 远端分化是必需的（从小鼠胚胎推断，Kobayashi et al. 2005），POU3F3 参与亨氏袢的延伸和远端小管的形成（从小鼠胚胎推断，Nakai et al. 2003）。肾囊泡的近端区域表达 WT1，直接抑制 PAX2，从而允许足细胞形成（从小鼠同源物推断，Ryan et al. 1995）。肾囊泡发育成逗号状体，其中 HNF1B 在远端区域激活 NOTCH 通路组件 DLL1、JAG1 和 LFNG（从小鼠胚胎推断，Heliot et al. 2013）。逗号状体随后发育成 S 形体，其中 HNF1B 激活 IRX1 和 IRX2 在中间区域（从小鼠胚胎推断，Heliot et al. 2013）。足细胞、近端小管、中间小管和远端小管随后分化。
英文描述
Nephron development A nephron of an amniote such as mouse or human comprises the glomerulus where small molecules are filtered out of the blood, the proximal tubule and the loop of Henle where small molecules are selectively reabsorbed, the thick ascending limb, the macula densa, the distal convoluted tubule, the connecting tubule, and the collecting duct which drains into the ureter.
Initiation of nephron development occurs at the termini of the branches of the ureteric bud where cells of the ureteric bud interact with cells of the metanephric mesenchyme. Rather than differentiating in place, analysis of cellular migration indicates that progenitors are recruited from the mesenchyme to the developing epithelial elements of the nephron (Lindstrom et al. 2018). The transcriptional program that operates during human nephrogenesis has been mapped in extraordinary detail (Lindstrom et al. 2021). WNT9B secreted by the ureteric bud induces a subset of renal progenitor cells to aggregate and express WNT4, which causes the pre-tubular aggregates to further undergo a mesenchymal to epithelial transition to form renal vesicles (inferred from mouse embryos in Park et al. 2007, reviewed in El-Dahr et al. 2008, Costantini and Kopan 2010, Desgrange and Cereghini 2015). A subset of renal progenitor cells express SIX2 and respond to WNT9B by proliferating to maintain a renewing population of renal progenitors. The reason for the difference in responses may be the local concentration of WNT9B (inferred from mouse embryos in Ramalingam et al. 2018) or the presence of the transcription factor SIX2 (inferred from mouse embryos in Karner et al. 2011).
The renal vesicle becomes polarized early. The distal region contains a gene regulatory network containing LHX1, POU3F3 (BRN1), DLL1, and JAG1. LHX1 is required for proximo-distal differentiation (inferred from mouse embryos in Kobayashi et al. 2005) and POU3F3 participates in elongation of the loop of Henle and formation of the distal convoluted tubule (inferred from mouse embryos in Nakai et al. 2003). The proximal region of the renal vesicle expresses WT1, which directly represses PAX2 to enable formation of podocytes (inferred from mouse homologs in Ryan et al. 1995). The renal vesicle develops into the comma-shaped body in which HNF1B in the distal region activates NOTCH pathway components DLL1, JAG1, and LFNG (inferred from mouse embryos in Heliot et al. 2013). The comma-shaped body in turn develops into the S-shaped body in which HNF1B activates IRX1 and IRX2 in the intermediate region (inferred from mouse embryos in Heliot et al. 2013). Podocytes, the proximal tubule, the intermediate tubule, and the distal tubule then differentiate.
Initiation of nephron development occurs at the termini of the branches of the ureteric bud where cells of the ureteric bud interact with cells of the metanephric mesenchyme. Rather than differentiating in place, analysis of cellular migration indicates that progenitors are recruited from the mesenchyme to the developing epithelial elements of the nephron (Lindstrom et al. 2018). The transcriptional program that operates during human nephrogenesis has been mapped in extraordinary detail (Lindstrom et al. 2021). WNT9B secreted by the ureteric bud induces a subset of renal progenitor cells to aggregate and express WNT4, which causes the pre-tubular aggregates to further undergo a mesenchymal to epithelial transition to form renal vesicles (inferred from mouse embryos in Park et al. 2007, reviewed in El-Dahr et al. 2008, Costantini and Kopan 2010, Desgrange and Cereghini 2015). A subset of renal progenitor cells express SIX2 and respond to WNT9B by proliferating to maintain a renewing population of renal progenitors. The reason for the difference in responses may be the local concentration of WNT9B (inferred from mouse embryos in Ramalingam et al. 2018) or the presence of the transcription factor SIX2 (inferred from mouse embryos in Karner et al. 2011).
The renal vesicle becomes polarized early. The distal region contains a gene regulatory network containing LHX1, POU3F3 (BRN1), DLL1, and JAG1. LHX1 is required for proximo-distal differentiation (inferred from mouse embryos in Kobayashi et al. 2005) and POU3F3 participates in elongation of the loop of Henle and formation of the distal convoluted tubule (inferred from mouse embryos in Nakai et al. 2003). The proximal region of the renal vesicle expresses WT1, which directly represses PAX2 to enable formation of podocytes (inferred from mouse homologs in Ryan et al. 1995). The renal vesicle develops into the comma-shaped body in which HNF1B in the distal region activates NOTCH pathway components DLL1, JAG1, and LFNG (inferred from mouse embryos in Heliot et al. 2013). The comma-shaped body in turn develops into the S-shaped body in which HNF1B activates IRX1 and IRX2 in the intermediate region (inferred from mouse embryos in Heliot et al. 2013). Podocytes, the proximal tubule, the intermediate tubule, and the distal tubule then differentiate.
所含基因
10 个基因