Neuronatin promotes neural lineage in ESCs via Ca(2+) signaling.
Neuronatin promotes neural lineage in ESCs via Ca(2+) signaling.
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DOI：
10.1002/stem.530
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发表时间：
2010-11
期刊：
影响因子：
5.2
通讯作者：
Sun, Yuh-Man
中科院分区：
文献类型：
--
作者：
Lin, Hsuan-Hwai;Bell, Esther;Uwanogho, Dafe;Perfect, Leo W.;Noristani, Harun;Bates, Thomas J. D.;Snetkov, Vladimir;Price, Jack;Sun, Yuh-Man
神经诱导是脊椎动物中枢神经系统形成的第一步。神经诱导机制的新共识是抑制骨形态发生蛋白（BMP）信号和激活成纤维细胞生长因子(FGF)/Erk信号的综合影响，它们通过自分泌或旁分泌的方式在外部起作用。然而，内在力量（线索）是否存在，它们是否在神经诱导中起决定性作用？这些问题还有待回答。在这里，我们已经确定了一种新的神经启动器，神经元蛋白（Nnat），它是促进哺乳动物和爪蟾神经命运的内在因素。尽管BMP通路受到抑制，但缺乏这种内在因子的ESCs不能进行神经诱导。研究表明，Nnat通过拮抗内质网Ca2+- atp酶异构体2 (sarco/内质网Ca2+- atp酶异构体2)，增加细胞内Ca2+ ([Ca2+]i)，从而启动ESCs的神经诱导，从而增加Erk1/2的磷酸化，抑制BMP4途径，并与FGF/Erk途径一起导致神经诱导。干细胞2010；28:1950 - 1960
Neural induction is the first step in the formation of the vertebrate central nervous system. The emerging consensus of the mechanisms underling neural induction is the combined influences from inhibiting bone morphogenetic protein (BMP) signaling and activating fibroblast growth factor (FGF)/Erk signaling, which act extrinsically via either autocrine or paracrine fashions. However, do intrinsic forces (cues) exist and do they play decisive roles in neural induction? These questions remain to be answered. Here, we have identified a novel neural initiator, neuronatin (Nnat), which acts as an intrinsic factor to promote neural fate in mammals and Xenopus. ESCs lacking this intrinsic factor fail to undergo neural induction despite the inhibition of the BMP pathway. We show that Nnat initiates neural induction in ESCs through increasing intracellular Ca2+ ([Ca2+]i) by antagonizing Ca2+-ATPase isoform 2 (sarco/endoplasmic reticulum Ca2+-ATPase isoform 2) in the endoplasmic reticulum, which in turn increases the phosphorylation of Erk1/2 and inhibits the BMP4 pathway and leads to neural induction in conjunction with FGF/Erk pathway. STEM CELLS 2010;28:1950–1960
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DOI：
10.1016/j.devbrainres.2004.03.016
发表时间：
2004-07-19
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Creton, R
通讯作者：
Creton, R
DOI：
10.1073/pnas.1734197100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Aubert, J;Stavridis, MP;Smith, A
通讯作者：
Smith, A
影响因子：
25
作者：
Bibel, M;Richter, J;Barde, YA
通讯作者：
Barde, YA
影响因子：
2.7
作者：
Cohen, Malkiel A.;Itsykson, Pavel;Reubinoff, Benjamin E.
通讯作者：
Reubinoff, Benjamin E.
影响因子：
64.5
作者：
LIEM, KF;TREMML, G;JESSELL, TM
通讯作者：
JESSELL, TM