1. The Zinc Finger Transcription Factor Ovol2 Acts Downstream of the Bone Morphogenetic Protein Pathway to Regulate the Cell Fate Decision between Neuroectoderm and Mesendoderm*
- Author
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Lingyu Li, Ting Zhang, Yunbo Qiao, Qingqing Zhu, Naihe Jing, Zhihui Xie, and Yongfeng Chen
- Subjects
Mesoderm ,animal structures ,Cellular differentiation ,Smad Proteins ,Bone Morphogenetic Protein 4 ,Chick Embryo ,Cell fate determination ,Biology ,Bone morphogenetic protein ,Biochemistry ,Avian Proteins ,Mice ,medicine ,Animals ,Humans ,Molecular Biology ,Neural cell ,Neural Plate ,Neuroectoderm ,SOXB1 Transcription Factors ,Endoderm ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Embryo, Mammalian ,Molecular biology ,Cell biology ,medicine.anatomical_structure ,Bone morphogenetic protein 4 ,Gene Knockdown Techniques ,embryonic structures ,Chickens ,Neural plate ,Signal Transduction ,Transcription Factors - 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.
- Published
- 2013