title: The zinc finger transcription factor Ovol2 acts downstream of the bone morphogenetic protein pathway to regulate the cell fate decision between neuroectoderm and mesendoderm.
abstract: During early embryonic development, bone morphogenetic protein (BMP) signaling is essential for neural/non-neural cell fate decisions. BMP signaling inhibits precocious neural differentiation and allows for proper differentiation of mesoderm, endoderm, and epidermis. However, the mechanisms underlying the BMP pathway-mediated cell fate decision remain largely unknown. Here, we show that the expression of Ovol2, which encodes an evolutionarily conserved zinc finger transcription factor, is down-regulated during neural differentiation of mouse embryonic stem cells. Knockdown of Ovol2 in embryonic stem cells facilitates neural conversion and inhibits mesendodermal differentiation, whereas Ovol2 overexpression gives rise to the opposite phenotype. Moreover, Ovol2 knockdown partially rescues the neural inhibition and mesendodermal induction by BMP4. Mechanistic studies further show that BMP4 directly regulates Ovol2 expression through the binding of Smad1/5/8 to the second intron of the Ovol2 gene. In the chick embryo, cOvol2 expression is specifically excluded from neural territory and is up-regulated by BMP4. In addition, ectopic expression of cOvol2 in the prospective neural plate represses the expression of the definitive neural plate marker cSox2. Taken together, these results indicate that Ovol2 acts downstream of the BMP pathway in the cell fate decision between neuroectoderm and mesendoderm to ensure proper germ layer development.
authors: 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: Ting
authors: T
authors: Zhang
authors: Qingqing
authors: Q
authors: Zhu
authors: Zhihui
authors: Z
authors: Xie
authors: Yongfeng
authors: Y
authors: Chen
authors: Yunbo
authors: Y
authors: Qiao
authors: Lingyu
authors: L
authors: Li
authors: Naihe
authors: N
authors: Jing
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D054258:Neural Plate / Q000166:cytology / Q000196:embryology*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C491431:MOVO protein, mouse; D055748:SOXB1 Transcription Factors; D051785:Smad Proteins; C527783:Sox2 protein, mouse; D014157:Transcription Factors