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上海生科院:BMP信号通路成胚胎外胚层模式命运决定者

时间:2012-11-25 浏览次数:1205

摘要:

BMP信号通路在神经发育的过程中发挥着极为重要的作用,2012年9月4日,中国科学院上海生科院生化与细胞所景乃禾课题组发现了BMP信号通路相关下游靶基因AP2γ,证实了AP2γ基因是高等动物早期胚胎神经发育的决定因素。

 
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9月4日,上海生科院生化与细胞所景乃禾研究组的揭示了一个新的BMP信号通路下游靶基因AP2γ,并发现该基因参与调控高等动物早期胚胎外胚层模式建成中神经和表皮的命运决定。这篇题为 “AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning"在线发表在学术期刊Cell Research上。

景乃禾研究组博士研究生乔云波及其同事通过基因芯片筛选BMP信号的响应因子,并进一步证明AP2γ是BMP信号通路的直接下游靶基因。功能研究发现,在胚胎干细胞的分化过程中,AP2γ能够抑制其向神经分化而促进细胞的表皮命运决定,并且AP2γ能够部分介导BMP信号抑制神经和促进表皮分化的功能;早期鸡胚中的研究发现,AP2γ的表达模式呈动态的变化,即从整个上胚层逐步迁移到表皮外胚层,迁移的过程中,AP2γ的表达与早期的神经板标记基因Sox2的表达区域呈互补关系。功能实验发现,在中间神经板AP2γ介导BMP的功能抑制神经板的过份扩展和神经的提前发生,而在表皮外胚层AP2γ能够作为BMP的下游基因促进表皮的发育。这一工作揭示了BMP信号在早期发育中,如何通过核内转录因子抑制神经的提前发生,从而保障神经发育进程的正常进行。

此科研项目由科技部、国家自然科学基金委员会以及中国科学

哺乳动物的早期神经发育是一个严谨而有序的过程,近年来的研究发现BMP信号通路在外胚层向神经和表皮分化过程中发挥了极其重要的功能,小鼠中的研究表明BMP信号能够抑制神经的提前发生,但是BMP发挥功能的分子机制却知之甚少。

此科研项目由科技部、国家自然科学基金委员会以及中国科学院的资助。

BMP信号通路成胚胎外胚层模式命运决定者

原文摘要:

AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning.

Qiao Y, Zhu Y, Sheng N, Chen J, Tao R, Zhu Q, Zhang T, Qian C, Jing N.

Bone morphogenetic protein (BMP) inhibits neural specification and induces epidermal differentiation during ectodermal patterning. However, the mechanism of this process is not well understood. Here we show that AP2γ, a transcription factor activator protein (AP)-2 family member, is upregulated by BMP4 during neural differentiation of pluripotent stem cells. Knockdown of AP2γ facilitates mouse embryonic stem cell (ESC) neural fate determination and impairs epidermal differentiation, whereas AP2γ overexpression inhibits neural conversion and promotes epidermal commitment. In the early chick embryo, AP2γ is expressed in the entire epiblast before HH stage 3 and gradually shifts to the putative epidermal ectoderm during HH stage 4. In the future neural plate AP2γ inhibits excessive neural expansion and it also promotes epidermal development in the surface ectoderm. Moreover, AP2γ knockdown in ESCs and chick embryos partially rescued the neural inhibition and epidermal induction effects of BMP4. Mechanistic studies showed that BMP4 directly regulates AP2γ expression through Smad1 binding to the AP2γ promoter. Taken together, we propose that during the early stages of ectodermal patterning in the chick embryo, AP2γ acts downstream of the BMP pathway to restrict precocious neural expansion in the prospective neural plate and initiates epidermal differentiation in the future epidermal ectoderm

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