Trophoblast lineage specific expression of the alternative splicing factor RBFOX2 suggests a role in placental development
| Autor: | Ilana Ariel, Simcha Yagel, Polina Denichenko, Caryn Greenfield, Debra Goldman-Wohl, Amina Jbara, Iris Eisenberg-Loebl, Rotem Karni |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Primary Cell Culture Biology 03 medical and health sciences Exon 0302 clinical medicine Syncytiotrophoblast Pregnancy Placenta medicine Humans Cell Lineage reproductive and urinary physiology Gene knockdown 030219 obstetrics & reproductive medicine Cytotrophoblast Cell fusion Alternative splicing Obstetrics and Gynecology Trophoblast Placentation Cell biology Trophoblasts Repressor Proteins 030104 developmental biology medicine.anatomical_structure Reproductive Medicine embryonic structures Female RNA Splicing Factors Developmental Biology |
| Zdroj: | Placenta. 100 |
| ISSN: | 1532-3102 |
| Popis: | Introduction RBFOX2, an RNA-binding protein, controls tissue-specific alternative splicing of exons in diverse processes of development. The progenitor cytotrophoblast of the human placenta differentiates into either the syncytiotrophoblast, formed via cell fusion, or the invasive extravillous trophoblast lineage. The placenta affords a singular system where a role for RBFOX2 in both cell invasion and cell fusion may be studied. We investigated a role for RBFOX2 in trophoblast cell differentiation, as a foundation for investigations of RBFOX2 in embryo implantation and placental development. Methods Immunohistochemistry of RBFOX2 was performed on placental tissue sections from three trimesters of pregnancy and from pathological pregnancies. Primary trophoblast cell culture and immunofluorescence were employed to determine RBFOX2 expression upon cell fusion. Knockdown of RBFOX2 expression was performed with βhCG and syncytin-1 as molecular indicators of fusion. Results In both normal and pathological placentas, RBFOX2 expression was confined to the cytotrophoblast and the extravillous trophoblast, but absent from the syncytiotrophoblast. Additionally, we showed that primary trophoblasts that spontaneously fused in cell culture downregulated RBFOX2 expression. In functional experiments, knockdown expression of RBFOX2 significantly upregulated βhCG, while the upregulation of syncytin-1 did not reach statistical significance. Discussion RBFOX2, by conferring mRNA diversity, may act as a regulator switch in trophoblast differentiation to either the fusion or invasive pathways. By studying alternative splicing we further our understanding of placental development, yielding possible insights into preeclampsia, where expression of antiangiogenic isoforms produced through alternative splicing play a critical role in disease development and severity. |
| Databáze: | OpenAIRE |
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