Timing is everything: Reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis.

Timing is everything: Reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis.
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时机就是一切:重申的Wnt,BMP和RA信号传导调节内胚剂器官发生过程中的发育能力。

DOI:
10.1016/j.ydbio.2017.11.018
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发表时间:
2018-02-01
影响因子:
2.7
通讯作者:
Zorn AM
Zorn AM
中科院分区:
生物学3区
文献类型:
--
作者:
Rankin SA;McCracken KW;Luedeke DM;Han L;Wells JM;Shannon JM;Zorn AM

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在器官发生过程中,少量的信号通路被重复使用,并且它们可以根据胚胎阶段对相同的细胞群体产生截然不同的影响。细胞能力如何随着发育时间的变化还不清楚。在这里,我们使用非洲爪蟾,小鼠和人类多能干细胞,以调查如何的时间序列的Wnt,BMP和视黄酸(RA)信号调节内胚层发育能力和器官诱导,重点呼吸的命运。虽然Nkx 2 -1+肺的命运是不诱导,直到后期的体节发生阶段,在这里,我们表明,肺的能力是由原肠胚阶段的Wnt和BMP依赖的前后(A-P)图案的结果限制。这些早期Wnt和BMP信号使后内胚层对随后的RA/Wnt/BMP依赖性肺诱导不敏感。我们进一步绘制了RA如何以时间特异性方式调节对Wnt和BMP的反应。在原肠胚RA促进后身份,然而,在早期体节发育阶段RA调节呼吸与咽电位在前内胚层和中肠与后肠电位在后内胚层。总之,我们的数据表明脊椎动物内胚层在器官发生过程中的动态和保守的反应,其中早期Wnt/BMP/RA影响细胞如何响应后来的Wnt/BMP/RA信号,说明如何交替组合信号可以调节发育能力和随后的命运规范。
A small number of signaling pathways are used repeatedly during organogenesis, and they can have drastically different effects on the same population of cells depending on the embryonic stage. How cellular competence changes over developmental time is not well understood. Here we used Xenopus, mouse, and human pluripotent stem cells to investigate how the temporal sequence of Wnt, BMP, and retinoic acid (RA) signals regulates endoderm developmental competence and organ induction, focusing on respiratory fate. While Nkx2-1+ lung fate is not induced until late somitogenesis stages, here we show that lung competence is restricted by the gastrula stage as a result of Wnt and BMP-dependent anterior-posterior (A-P) patterning. These early Wnt and BMP signals make posterior endoderm refractory to subsequent RA/Wnt/BMP-dependent lung induction. We further mapped how RA modulates the response to Wnt and BMP in a temporal specific manner. In the gastrula RA promotes posterior identity, however in early somite stages of development RA regulates respiratory versus pharyngeal potential in anterior endoderm and midgut versus hindgut potential in posterior endoderm. Together our data suggest a dynamic and conserved response of vertebrate endoderm during organogenesis, wherein early Wnt/BMP/RA impacts how cells respond to later Wnt/BMP/RA signals, illustrating how reiterative combinatorial signaling can regulate both developmental competence and subsequent fate specification.
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