Lineage tracing of axial progenitors using Nkx1-2CreER(T2) mice defines their trunk and tail contributions.

Lineage tracing of axial progenitors using Nkx1-2CreER(T2) mice defines their trunk and tail contributions.
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DOI:
10.1242/dev.164319
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发表时间:
2018-10-02
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Storey KG
Storey KG
中科院分区:
其他
文献类型:
--
作者:
Rodrigo Albors A;Halley PA;Storey KG

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脊椎动物的身体是由胚胎后端的祖细胞不断产生新组织而形成的。这些轴向祖细胞的研究已被证明是具有挑战性的,在体内主要是因为缺乏独特的分子标记来识别它们。在这里,我们阐明了转录因子Nkx 1 -2在小鼠胚胎中的表达模式,并表明它识别整个身体轴伸长轴祖细胞,包括神经中胚层祖细胞和早期神经和中胚层祖细胞。我们创建了一个他莫昔芬诱导的Nkx 1 - 2CreERT 2转基因小鼠,并利用这条线的条件性质,以揭示在特定阶段的Nkx 1 -2表达细胞的谱系贡献。我们发现,早期Nkx 1 -2表达的上胚层细胞有助于所有三个胚层,主要是神经外胚层和中胚层,不包括脊索。我们的数据是一致的存在下,一些自我更新的轴向祖细胞,继续产生神经和中胚层组织的尾芽。这项研究确定了Nkx 1 -2表达细胞的来源,在小鼠的躯干和尾部组织,并提供了一个有用的工具,在体内遗传标记和操纵轴向祖细胞。总结:使用内源性Nkx 1 -2启动子控制下的他莫昔芬诱导的Cre系揭示了轴向祖细胞对发育中小鼠胚胎的谱系贡献的变化。
The vertebrate body forms by continuous generation of new tissue from progenitors at the posterior end of the embryo. The study of these axial progenitors has proved to be challenging in vivo largely because of the lack of unique molecular markers to identify them. Here, we elucidate the expression pattern of the transcription factor Nkx1-2 in the mouse embryo and show that it identifies axial progenitors throughout body axis elongation, including neuromesodermal progenitors and early neural and mesodermal progenitors. We create a tamoxifen-inducible Nkx1-2CreERT2 transgenic mouse and exploit the conditional nature of this line to uncover the lineage contributions of Nkx1-2-expressing cells at specific stages. We show that early Nkx1-2-expressing epiblast cells contribute to all three germ layers, mostly neuroectoderm and mesoderm, excluding notochord. Our data are consistent with the presence of some self-renewing axial progenitors that continue to generate neural and mesoderm tissues from the tail bud. This study identifies Nkx1-2-expressing cells as the source of most trunk and tail tissues in the mouse and provides a useful tool to genetically label and manipulate axial progenitors in vivo. Summary: Changing lineage contributions of axial progenitors to the developing mouse embryo are revealed using a tamoxifen-inducible Cre line under the control of the endogenous Nkx1-2 promoter.
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