Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells.
Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells.
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DOI：
10.1242/bio.20149977
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发表时间：
2015-03-06
期刊：
影响因子：
2.4
通讯作者：
Viczian AS
中科院分区：
文献类型：
--
作者：
Wong KA;Trembley M;Abd Wahab S;Viczian AS
视网膜的形成需要关键调控因子的正确时空模式。虽然已知几种信号传导途径的抑制导致视网膜命运的特化，但仅添加Noggin（一种已知的BMP拮抗剂）可以将多能非洲爪蟾动物帽细胞转化为功能性视网膜细胞。本研究的目的是确定在这种转换过程中发生的细胞内分子事件。令人惊讶的是，单独阻断BMP信号传导未能模拟头蛋白处理。在多能细胞中过度表达Noggin导致Smad 1和Smad 2磷酸化的浓度依赖性抑制，这两种磷酸化分别作用于BMP和激活素信号传导的下游。这导致下游靶点减少：内皮标记物xk 81和中胚层标记物xbra。我们用显性负性受体或化学抑制剂dorsomorphin和SB 431542处理多能细胞，它们各自靶向BMP或激活素信号通路。我们使用动物帽移植（ACT）测定确定这些治疗对视网膜形成的影响;其中将经治疗的多能细胞移植到宿主胚胎的眼区中。我们发现，在BMP信号传导抑制的存在下，激活素信号传导的抑制促进爪蟾组织中有效的视网膜特化，模拟单独添加头蛋白的影响。在整个胚胎中，我们发现眼区标记rax在添加显性负性Smad 1和Smad 2时扩大，用dorsomorphin和SB 431542处理细胞也是如此。未来的研究可以将这些发现转化为哺乳动物培养试验，以便更有效地在培养中产生视网膜细胞。
Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT) assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture.
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影响因子：
5.4
作者：
Heinecke K;Seher A;Schmitz W;Mueller TD;Sebald W;Nickel J
通讯作者：
Nickel J
影响因子：
9.8
作者：
Kuroda H;Wessely O;De Robertis EM
通讯作者：
De Robertis EM
DOI：
10.1007/bf00383771
发表时间：
1990-01-01
期刊：
ROUXS ARCHIVES OF DEVELOPMENTAL BIOLOGY
影响因子：
--
作者：
ASASHIMA, M;NAKANO, H;UENO, N
通讯作者：
UENO, N
影响因子：
64.5
作者：
Eppert, K;Scherer, SW;Attisano, L
通讯作者：
Attisano, L
影响因子：
2.7
作者：
Hoodless, PA;Tsukazaki, T;Thomsen, GH
通讯作者：
Thomsen, GH