Naylor Richard W, Qubisi Sarah S, Davidson Alan J
Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Results Probl Cell Differ. 2017;60:27-53. doi: 10.1007/978-3-319-51436-9_2.
The pronephros is the first kidney type to form in vertebrate embryos. The first step of pronephrogenesis in the zebrafish is the formation of the intermediate mesoderm during gastrulation, which occurs in response to secreted morphogens such as BMPs and Nodals. Patterning of the intermediate mesoderm into proximal and distal cell fates is induced by retinoic acid signaling with downstream transcription factors including wt1a, pax2a, pax8, hnf1b, sim1a, mecom, and irx3b. In the anterior intermediate mesoderm, progenitors of the glomerular blood filter migrate and fuse at the midline and recruit a blood supply. More posteriorly localized tubule progenitors undergo epithelialization and fuse with the cloaca. The Notch signaling pathway regulates the formation of multi-ciliated cells in the tubules and these cells help propel the filtrate to the cloaca. The lumenal sheer stress caused by flow down the tubule activates anterior collective migration of the proximal tubules and induces stretching and proliferation of the more distal segments. Ultimately these processes create a simple two-nephron kidney that is capable of reabsorbing and secreting solutes and expelling excess water-processes that are critical to the homeostasis of the body fluids. The zebrafish pronephric kidney provides a simple, yet powerful, model system to better understand the conserved molecular and cellular progresses that drive nephron formation, structure, and function.
前肾是脊椎动物胚胎中形成的第一种肾脏类型。斑马鱼前肾发生的第一步是在原肠胚形成过程中形成中间中胚层，这是对诸如骨形态发生蛋白（BMPs）和结节蛋白（Nodals）等分泌的形态发生素作出的反应。视黄酸信号与包括wt1a、pax2a、pax8、hnf1b、sim1a、mecom和irx3b在内的下游转录因子一起诱导中间中胚层分化为近端和远端细胞命运。在前侧中间中胚层中，肾小球滤过器的祖细胞迁移并在中线融合，募集血液供应。更靠后的肾小管祖细胞发生上皮化并与泄殖腔融合。Notch信号通路调节肾小管中多纤毛细胞的形成，这些细胞有助于将滤液推进到泄殖腔。沿肾小管流动引起的管腔内剪切应力激活近端肾小管的前向集体迁移，并诱导更远端节段的伸展和增殖。最终，这些过程形成了一个简单的双肾单位肾脏，它能够重吸收和分泌溶质并排出多余的水分，这些过程对于体液平衡至关重要。斑马鱼的前肾提供了一个简单而强大的模型系统，以更好地理解驱动肾单位形成、结构和功能的保守分子和细胞过程。
