9月4日,，國際學(xué)術(shù)期刊Cell Research在線發(fā)表了上海生科院生化與細(xì)胞所景乃禾研究組的研究論文 “AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning",。該論文發(fā)現(xiàn)了一個(gè)新的BMP信號(hào)通路下游靶基因AP2g，并發(fā)現(xiàn)該基因參與調(diào)控高等動(dòng)物早期胚胎外胚層模式建成中神經(jīng)和表皮的命運(yùn)決定,。
哺乳動(dòng)物的早期神經(jīng)發(fā)育是一個(gè)嚴(yán)謹(jǐn)而有序的過程，近年來的研究發(fā)現(xiàn)BMP信號(hào)通路在外胚層向神經(jīng)和表皮分化過程中發(fā)揮了極其重要的功能，小鼠中的研究表明BMP信號(hào)能夠抑制神經(jīng)的提前發(fā)生,，但是BMP發(fā)揮功能的分子機(jī)制卻知之甚少,。
景乃禾研究組博士研究生喬云波及其同事通過基因芯片篩選BMP信號(hào)的響應(yīng)因子，并進(jìn)一步證明AP2γ是BMP信號(hào)通路的直接下游靶基因,。功能研究發(fā)現(xiàn),，在胚胎干細(xì)胞的分化過程中，AP2γ能夠抑制其向神經(jīng)分化而促進(jìn)細(xì)胞的表皮命運(yùn)決定,，并且AP2γ能夠部分介導(dǎo)BMP信號(hào)抑制神經(jīng)和促進(jìn)表皮分化的功能,；早期雞胚中的研究發(fā)現(xiàn)，AP2γ的表達(dá)模式呈動(dòng)態(tài)的變化,，即從整個(gè)上胚層逐步遷移到表皮外胚層,，遷移的過程中，AP2γ的表達(dá)與早期的神經(jīng)板標(biāo)記基因Sox2的表達(dá)區(qū)域呈互補(bǔ)關(guān)系,。功能實(shí)驗(yàn)發(fā)現(xiàn),，在中間神經(jīng)板AP2γ介導(dǎo)BMP的功能抑制神經(jīng)板的過份擴(kuò)展和神經(jīng)的提前發(fā)生，而在表皮外胚層AP2γ能夠作為BMP的下游基因促進(jìn)表皮的發(fā)育,。這一工作揭示了BMP信號(hào)在早期發(fā)育中,，如何通過核內(nèi)轉(zhuǎn)錄因子抑制神經(jīng)的提前發(fā)生，從而保障神經(jīng)發(fā)育進(jìn)程的正常進(jìn)行,。
該研究項(xiàng)目得到了科技部,、國家自然科學(xué)基金委和中國科學(xué)院的資助。（生物谷Bioon.com）
doi:10.1038/cr.2012.122
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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.
Abstract
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.
