Transcription factor TFAP2B up-regulates human corneal endothelial cell–specific genes during corneal development and maintenance

Abstract

The corneal endothelium, which originates from the neural crest via the periocular mesenchyme (PM), is crucial for maintaining corneal transparency. The development of corneal endothelial cells (CECs) from the neural crest is accompanied by the expression of several transcription factors, but the contribution of some of these transcriptional regulators to CEC development is incompletely understood. Here, we focused on activating enhancer-binding protein 2 (TFAP2, AP-2), a neural crest-expressed transcription factor. Using semiquantitative/quantitative RT-PCR and reporter gene and biochemical assays, we found that, within the AP-2 family, the TFAP2B gene is the only one expressed in human CECs in vivo and that its expression is strongly localized to the peripheral region of the corneal endothelium. Furthermore, the TFAP2B protein was expressed both in vivo and in cultured CECs. During mouse development, TFAP2B expression began in the PM at embryonic day 11.5 and then in CECs during adulthood. siRNA-mediated knockdown of TFAP2B in CECs decreased the expression of the corneal endotheliumspecific proteins type VIII collagen ␣2 (COL8A2) and zona pellucida glycoprotein 4 (ZP4) and suppressed cell proliferation. Of note, we also found that TFAP2B binds to the promoter of the COL8A2 and ZP4 genes. Furthermore, CECs that highly expressed ZP4 also highly expressed both TFAP2B and COL8A2 and showed high cell proliferation. These findings suggest that TFAP2B transcriptionally regulates CEC-specific genes and therefore may be an important transcriptional regulator of corneal endothelial development and homeostasis. This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grants 15K20259 and JP 17K169680. The authors declare that they have no conflicts of interest with the contents of this article. This article contains Tables S1 and S2.

Directed Differentiation of Human Pluripotent Stem Cells towards Corneal Endothelial-Like Cells under Defined Conditions

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TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway

“…Resent studies showed that TFAP2B as one of the corneal endothelial-specific transcription factors 29 , and identified ZP4 as a target gene of TFAP2B, TFAP2B could bind to the ZP4 promoter region and directly induce the expression of the ZP4 protein 30 . In our study, TFAP2B expression was high in papillary thyroid cancer cell lines compared with normal cells and in tumor tissues compared with tissues adjacent to tumors.…”

The Use of Induced Pluripotent Stem Cells as a Model for Developmental Eye Disorders

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