上海生科院：BMP信號(hào)通路成胚胎外胚層模式命運(yùn)決定者
更新時(shí)間：2012-11-25 瀏覽次數(shù)：1943
| 摘要： BMP信號(hào)通路在神經(jīng)發(fā)育的過(guò)程中發(fā)揮著極為重要的作用，2012年9月4日，中國(guó)科學(xué)院上海生科院生化與細(xì)胞所景乃禾課題組發(fā)現(xiàn)了BMP信號(hào)通路相關(guān)下游靶基因AP2γ，證實(shí)了AP2γ基因是高等動(dòng)物早期胚胎神經(jīng)發(fā)育的決定因素。 | 被過(guò)濾廣告 |
9月4日，上海生科院生化與細(xì)胞所景乃禾研究組的揭示了一個(gè)新的BMP信號(hào)通路下游靶基因AP2γ，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。這篇題為 “AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning"在線發(fā)表在學(xué)術(shù)期刊Cell Research上。
景乃禾研究組博士研究生喬云波及其同事通過(guò)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(guò)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(guò)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(guò)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(guò)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。
此科研項(xiàng)目由科技部、國(guó)家自然科學(xué)基金委員會(huì)以及中國(guó)科學(xué)
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(guò)程，近年來(lái)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(guò)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。
此科研項(xiàng)目由科技部、國(guó)家自然科學(xué)基金委員會(huì)以及中國(guó)科學(xué)院的資助。
原文摘要：
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