Tbx18 expression demarcates multipotent precursor populations in the developing urogenital system but is exclusively required within the ureteric mesenchymal lineage to suppress a renal stromal fate
Tbx18 expression demarcates multipotent precursor populations in the developing urogenital system but is exclusively required within the ureteric mesenchymal lineage to suppress a renal stromal fate
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DOI：
10.1016/j.ydbio.2013.04.036
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发表时间：
2013-08-01
影响因子：
2.7
通讯作者：
Kispert, Andreas
中科院分区：
文献类型：
--
作者：
Bohnenpoll, Tobias;Bettenhausen, Eva;Kispert, Andreas
哺乳动物的泌尿生殖系统来源于不同生殖组织的多能祖细胞。个体亚种群对成熟系统特定组成部分的贡献以及各自谱系的时空限制仍然没有得到很好的表征。在这里，我们使用比较表达分析，描绘亚区域内的发展中泌尿生殖系统表达的T-box转录因子基因Tbx 18。我们发现，Tbx 18是瞬时表达的上皮衬里和下jumper间充质的泌尿生殖嵴。在后肾发育开始时，Tbx 18表达发生在后肾和沃尔夫管之间的间充质带中，但随后限于远端输尿管柄周围的间充质。遗传谱系追踪显示，前Tbx 18（+）细胞的泌尿生殖嵴和后肾领域，大大有助于肾上腺和性腺，肾间质，输尿管和膀胱间充质。Tbx 18的缺失不影响肾上腺、性腺、膀胱和肾脏的分化。然而，输尿管分化受到严重干扰，因为间充质谱系采用间质而不是输尿管平滑肌的命运。DiI标记和组织重组实验表明，Tbx 18表达的限制，以前瞻性输尿管间充质不反映一个积极的冷凝过程，但由于特定的损失Tbx 18表达的间充质的范围内的信号从输尿管上皮。这些细胞或者形成肾间质，或者经历细胞凋亡，帮助将输尿管与其周围组织分离。我们发现，Tbx 18缺陷细胞不响应上皮细胞的信号，这表明Tbx 18需要prepattem输尿管间充质。我们的研究提供了新的见解泌尿生殖系祖细胞的分子多样性，并有助于了解输尿管间充质亚系的规格。(c)2013 Elsevier Inc. All rights reserved.
The mammalian urogenital system derives from multipotent progenitor cells of different germinal tissues. The contribution of individual sub-populations to specific components of the mature system, and the spatiotemporal restriction of the respective lineages have remained poorly characterized. Here, we use comparative expression analysis to delineate sub-regions within the developing urogenital system that express the T-box transcription factor gene Tbx18. We show that Tbx18 is transiently expressed in the epithelial lining and the subjacent mesenchyme of the urogenital ridge. At the onset of metanephric development Tbx18 expression occurs in a band of mesenchyme in between the metanephros and the Wolffian duct but is subsequently restricted to the mesenchyme surrounding the distal ureter stalk. Genetic lineage tracing reveals that former Tbx18(+) cells of the urogenital ridge and the metanephric field, contribute substantially to the adrenal glands and gonads, to the kidney stroma, the ureteric and the bladder mesenchyme. Loss of Tbx18 does not affect differentiation of the adrenal gland, the gonad, the bladder and the kidney. However, ureter differentiation is severely disturbed as the mesenchymal lineage adopts a stromal rather than a ureteric smooth muscle fate. DiI labeling and tissue recombination experiments show that the restriction of Tbx18 expression to the prospective ureteric mesenchyme does not reflect an active condensation process but is due to a specific loss of Tbx18 expression in the mesenchyme out of range of signals from the ureteric epithelium. These cells either contribute to the renal stroma or undergo apoptosis aiding in severing the ureter from its surrounding tissues. We show that Tbx18-deficient cells do not respond to epithelial signals suggesting that Tbx18 is required to prepattem the ureteric mesenchyme. Our study provides new insights into the molecular diversity of urogenital progenitor cells and helps to understand the specification of the ureteric mesenchymal sub-lineage. (c) 2013 Elsevier Inc. All rights reserved.