Pinhead antagonizes Admp to promote notochord formation.
Pinhead antagonizes Admp to promote notochord formation.
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DOI：
10.1016/j.isci.2021.102520
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发表时间：
2021-06-25
期刊：
影响因子：
5.8
通讯作者：
Sokol SY
中科院分区：
文献类型：
--
作者：
Itoh K;Ossipova O;Sokol SY
脊椎动物胚胎的背腹侧模式严重依赖于Smad1的活性，Smad1介导BMP蛋白、抗背化形态发生蛋白（Admp）及其拮抗剂的信号传导。Pinhead （Pnhd）是一种含有半胱氨酸结的分泌蛋白，在爪蟾原肠胚形成过程中表达于腹外侧中胚层；然而，其分子靶点和信号机制尚未完全阐明。我们基于质谱的原肠泌素组筛选鉴定Admp为phd相关蛋白。我们发现Pnhd结合Admp并通过降低Smad1磷酸化及其转录靶点来抑制其腹化活性。重要的是，在Admp存在的情况下，Pnhd缺失进一步增加了phospho-Smad1水平。此外，Pnhd与Chordin和截断的BMP4受体协同诱导外胚层细胞的脊索标记物，Pnhd缺失的胚胎表现出脊索缺陷。我们的研究结果表明Pnhd结合Admp并使其失活以促进脊索发育。我们认为Admp和Pnhd之间的相互作用改善了脊椎动物原肠胚形成过程中Smad1的活性梯度。Pnhd与Chordin协同调节脊索发育。Pnhd和Admp的相互作用在背腹侧模式形成过程中改善Smad1信号传导。发育生物学;胚胎学
Dorsoventral patterning of a vertebrate embryo critically depends on the activity of Smad1 that mediates signaling by BMP proteins, anti-dorsalizing morphogenetic protein (Admp), and their antagonists. Pinhead (Pnhd), a cystine-knot-containing secreted protein, is expressed in the ventrolateral mesoderm during Xenopus gastrulation; however, its molecular targets and signaling mechanisms have not been fully elucidated. Our mass spectrometry-based screen of the gastrula secretome identified Admp as Pnhd-associated protein. We show that Pnhd binds Admp and inhibits its ventralizing activity by reducing Smad1 phosphorylation and its transcriptional targets. Importantly, Pnhd depletion further increased phospho-Smad1 levels in the presence of Admp. Furthermore, Pnhd synergized with Chordin and a truncated BMP4 receptor in the induction of notochord markers in ectoderm cells, and Pnhd-depleted embryos displayed notochord defects. Our findings suggest that Pnhd binds and inactivates Admp to promote notochord development. We propose that the interaction between Admp and Pnhd refines Smad1 activity gradients during vertebrate gastrulation. Mass spectrometry screen identifies Pnhd-binding proteins in the gastrula secretome Pnhd antagonizes Admp, a member of the BMP family, to reduce Smad1 phosphorylation Pnhd synergizes with Chordin to regulate notochord development The interaction of Pnhd and Admp refines Smad1 signaling during dorsoventral patterning Molecular biology; Developmental biology; Embryology
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影响因子：
64.5
作者：
Inomata, Hidehiko;Shibata, Tatsuo;Sasai, Yoshiki
通讯作者：
Sasai, Yoshiki
DOI：
10.1073/pnas.1203000109
发表时间：
2012-09-18
影响因子：
11.1
作者：
Inui, Masafumi;Montagner, Marco;Piccolo, Stefano
通讯作者：
Piccolo, Stefano
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
2.6
作者：
Dosch, R;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
4.6
作者：
Corallo, Diana;Schiavinato, Alvise;Bonaldo, Paolo
通讯作者：
Bonaldo, Paolo