The nephric mesenchyme lineage of intermediate mesoderm is derived from Tbx6-expressing derivatives of neuro-mesodermal progenitors via BMP-dependent Osr1 function
The nephric mesenchyme lineage of intermediate mesoderm is derived from Tbx6-expressing derivatives of neuro-mesodermal progenitors via BMP-dependent Osr1 function
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DOI：
10.1016/j.ydbio.2021.07.006
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发表时间：
2021-07-20
影响因子：
2.7
通讯作者：
Takemoto, Tatsuya
中科院分区：
文献类型：
--
作者：
Hayashi, Shinichi;Suzuki, Hitomi;Takemoto, Tatsuya
在脊椎动物胚胎中，肾原基后肾由两种不同的细胞谱系形成，沃尔夫管和后肾间充质，它们被经典地归类为中间中胚层。尽管这两种细胞群在肾脏发育中的相互作用已被广泛研究，但产生它们的机制仍然难以捉摸。在这里，我们表明，小鼠细胞谱系，形成肾间充质发展为一个亚群的Tbx 6表达中胚层前体衍生物的神经中胚层祖细胞（NMPs）的骨形态发生蛋白（BMP）信号依赖性Osr 1表达的条件下。表达Osr 1的肾间充质前体细胞被证实为NMPs的后代，因为它们被Sox 2 N1增强子-EGFP标记。在Tbx 6突变胚胎中，肾间充质改变其命运为神经组织，这反映了其NMP起源。在Osr 1突变体胚胎中，表达Tbx 6的中胚层前体的特定区域，通常表达Osr 1并发育成肾间充质，而不是表达体节标记FoxC 2。BMP信号在表达TBX 6的中胚层区域激活Osr 1表达，并引起肾间质发育。本研究提出了一种新的原肠胚形成过程中细胞谱系分离的模型。
In vertebrate embryos, the kidney primordium metanephros is formed from two distinct cell lineages, Wolffian duct and metanephric mesenchyme, which were classically grouped as intermediate mesoderm. Whereas the reciprocal interactions between these two cell populations in kidney development have been studied extensively, the mechanisms generating them remain elusive. Here, we show that the mouse cell lineage that forms nephric mesenchyme develops as a subpopulation of Tbx6-expressing mesodermal precursor derivatives of neuromesodermal progenitors (NMPs) under the condition of bone morphogenetic protein (BMP)-signal-dependent Osr1 expression. The Osr1-expressing nephric mesenchyme precursors were confirmed as descendants of NMPs because they were labeled by Sox2 N1 enhancer-EGFP. In Tbx6 mutant embryos, nephric mesenchyme changed its fate into neural tissues, which reflected its NMP origin. In Osr1 mutant embryos, the specific region of the Tbx6-expressing mesoderm precursor, which normally expresses Osr1 and develops into the nephric mesenchyme, instead expressed the somite marker FoxC2. BMP signaling activated Osr1 expression in a region of TBX6expressing mesoderm and elicited nephric mesenchyme development. This study suggested a new model of cell lineage segregation during gastrulation.