Renal development is a complex process in which two major processes, tubular branching and nephron development, regulate each other reciprocally. Our previous findings have indicated that collagen XVIII (ColXVIII), an extracellular matrix protein, affects the renal branching morphogenesis. We investigate here the role of ColXVIII in nephron formation and the behavior of nephron progenitor cells (NPCs) using isoform-specific ColXVIII knockout mice. The results show that the short ColXVIII isoform predominates in the early epithelialized nephron structures whereas the two longer isoforms are expressed only in the later phases of glomerular formation. Meanwhile, electron microscopy showed that the ColXVIII mutant embryonic kidneys have ultrastructural defects at least from embryonic day 16.5 onwards. Similar structural defects had previously been observed in adult ColXVIII-deficient mice, indicating a congenital origin. The lack of ColXVIII led to a reduced NPC population in which changes in NPC proliferation and maintenance and in macrophage influx were perceived to play a role. The changes in NPC behavior in turn led to notably reduced overall nephron formation. In conclusion, the results show that ColXVIII has multiple roles in renal development, both in ureteric branching and in NPC behavior.

中文翻译：

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XVIII 胶原蛋白调节发育中肾单位的细胞外基质完整性并影响肾单位祖细胞行为


肾脏发育是一个复杂的过程，其中两个主要过程（管状分支和肾单位发育）相互调节。我们之前的研究结果表明，细胞外基质蛋白 XVIII 胶原蛋白 (ColXVIII) 会影响肾分支形态发生。我们使用异构体特异性 ColXVIII 敲除小鼠研究 ColXVIII 在肾单位形成中的作用以及肾单位祖细胞 (NPC) 的行为。结果表明，短的 ColXVIII 亚型在早期上皮化肾单位结构中占主导地位，而两种较长的亚型仅在肾小球形成的后期阶段表达。同时，电子显微镜显示，ColXVIII突变体胚胎肾脏至少从胚胎第16.5天起就存在超微结构缺陷。之前在成年 ColXVIII 缺陷小鼠中观察到类似的结构缺陷，表明其具有先天性。 ColXVIII 的缺乏导致 NPC 数量减少，其中 NPC 增殖和维持以及巨噬细胞流入的变化被认为发挥了作用。 NPC 行为的变化反过来导致整体肾单位形成显着减少。总之，结果表明 ColXVIII 在肾脏发育中具有多种作用，包括输尿管分支和 NPC 行为。