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9月4日，上海生科院生化與細胞所景乃禾研究組的揭示了一個新的BMP信號通路下游靶基因AP2γ，并發現該基因參與調控高等動物早期胚胎外胚層模式建成中神經和表皮的命運決定。這篇題為 “AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning"在線發表在學術期刊Cell Research上。

景乃禾研究組博士研究生喬云波及其同事通過基因芯片篩選BMP信號的響應因子，并進一步證明AP2γ是BMP信號通路的直接下游靶基因。功能研究發現，在胚胎干細胞的分化過程中，AP2γ能夠抑制其向神經分化而促進細胞的表皮命運決定，并且AP2γ能夠部分介導BMP信號抑制神經和促進表皮分化的功能;早期雞胚中的研究發現，AP2γ的表達模式呈動態的變化，即從整個上胚層逐步遷移到表皮外胚層，遷移的過程中，AP2γ的表達與早期的神經板標記基因Sox2的表達區域呈互補關系。功能實驗發現，在中間神經板AP2γ介導BMP的功能抑制神經板的過份擴展和神經的提前發生，而在表皮外胚層AP2γ能夠作為BMP的下游基因促進表皮的發育。這一工作揭示了BMP信號在早期發育中，如何通過核內轉錄因子抑制神經的提前發生，從而保障神經發育進程的正常進行。

此科研項目由科技部、國家自然科學基金委員會以及中國科學

哺乳動物的早期神經發育是一個嚴謹而有序的過程，近年來的研究發現BMP信號通路在外胚層向神經和表皮分化過程中發揮了極其重要的功能，小鼠中的研究表明BMP信號能夠抑制神經的提前發生，但是BMP發揮功能的分子機制卻知之甚少。

此科研項目由科技部、國家自然科學基金委員會以及中國科學院的資助。

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