Glioma-associated Oncogene 2 Is Essential for Trophoblastic Fusion by Forming a Transcriptional Complex with Glial Cell Missing-a.

The Journal of Biological Chemistry
Chao TangXimei Wu

Abstract

Cell-cell fusion of human villous trophoblasts, referred to as a process of syncytialization, acts as a prerequisite for the proper development and functional maintenance of the human placenta. Given the fact that the main components of the Hedgehog signaling pathway are expressed predominantly in the syncytial layer of human placental villi, in this study, we investigated the potential roles and underlying mechanisms of Hedgehog signaling in trophoblastic fusion. Activation of Hedgehog signaling by a variety of approaches robustly induced cell fusion and the expression of syncytial markers, whereas suppression of Hedgehog signaling significantly attenuated cell fusion and the expression of syncytial markers in both human primary cytotrophoblasts and trophoblast-like BeWo cells. Moreover, among glioma-associated oncogene (GLI) family transcriptional factors in Hedgehog signaling, knockdown of GLI2 but not GLI1 and GLI3 significantly attenuated Hedgehog-induced cell fusion, whereas overexpression of the GLI2 activator alone was sufficient to induce cell fusion. Finally, GLI2 not only stabilized glial cell missing-a, a pivotal transcriptional factor for trophoblastic syncytialization, but also formed a transcriptional heterodimer...Continue Reading

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Citations

May 24, 2019·The Journal of Clinical Endocrinology and Metabolism·Hiroshi TakaiMasaki Mandai
Mar 5, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xiangzhi WangLanfang Tang
Oct 8, 2020·Hypertension·Andreas RitterJuping Yuan
Jan 5, 2021·Experimental & Molecular Medicine·Yibin PanSongying Zhang
Jun 27, 2021·Scientific Reports·Anil SigdelFrancisco Peñagaricano
Jul 14, 2021·Reproductive Sciences·Meiyuan JinChao Tang
Aug 16, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Haibin ZhuChao Tang

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