Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling
Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling
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DOI：
10.1242/dev.004234
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发表时间：
2007-05-15
期刊：
影响因子：
4.6
通讯作者：
Herzlinger, Doris
中科院分区：
文献类型：
--
作者：
Brenner-Anantharam, Andrea;Cebrian, Cristina;Herzlinger, Doris
尿路形态发生需要将输尿管芽（UB）细分为肾内集合系统和输尿管，这两种组织具有独特的结构和功能特性。在本报告中，我们研究了介导其分化的细胞和分子机制。发育中雏鸡的命运图谱实验表明，UB 被两个不同的间充质群体包围：源自中间中胚层的肾源性间充质和尾芽衍生的中胚层，后者选择性地与分化为输尿管的 UB 结构域相关。利用小鼠后肾肾外植体的功能实验表明，BMP4（一种由尾芽衍生的间充质分泌的旁分泌因子）是输尿管形态发生所必需的。相反，异位 BMP4 信号传导足以诱导 UB 域中的输尿管形态发生，该域通常注定分化为肾内集合系统。总的来说，这些结果表明肾脏和输尿管之间的边界形成于源自早期胚胎两个不同区域的间充质组织的交汇处。这些数据提出了一种可能性，即该连接对人类先天性缺陷（例如输尿管-骨盆阻塞）的敏感性可能与将来自这些不同谱系的细胞整合成单一功能结构所需的复杂形态发生运动有关。
Urinary tract morphogenesis requires the sub-division of the ureteric bud (UB) into the intra-renal collecting system and ureter, two tissues with unique structural and functional properties. In this report we investigate the cellular and molecular mechanisms that mediate their differentiation. Fate mapping experiments in the developing chick indicate that the UB is surrounded by two distinct mesenchymal populations: nephrogenic mesenchyme derived from the intermediate mesoderm and tailbud-derived mesoderm, which is selectively associated with the domain of the UB that differentiates into the ureter. Functional experiments utilizing murine metanephric kidney explants show that BMP4, a paracrine factor secreted by tailbud-derived mesenchyme, is required for ureter morphogenesis. Conversely, ectopic BMP4 signaling is sufficient to induce ureter morphogenesis in domains of the UB normally fated to differentiate into the intra-renal collecting system. Collectively, these results indicate that the border between the kidney and ureter forms where mesenchymal tissues originating in two different areas of the early embryo meet. These data raise the possibility that the susceptibility of this junction to congenital defects in humans, such as ureteral-pelvic obstructions, may be related to the complex morphogenetic movements that are required to integrate cells from these different lineages into a single functional structure.