title: AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning.
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.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Qiao
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.forename: Nengyin
authors.initials: N
authors.lastname: Sheng
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Naihe
authors.initials: N
authors.lastname: Jing
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002642:Chick Embryo; D004475:Ectoderm / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D004817:Epidermis / Q000196:embryology; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009420:Nervous System / Q000196:embryology*; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D034741:RNA, Small Interfering; D051898:Smad1 Protein; D050656:Transcription Factor AP-2