![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
Preview |
PDF (Supplementary Material)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
| Item Type: | Article |
|---|---|
| Title: | A Grhl2-dependent gene network controls trophoblast branching morphogenesis |
| Creators Name: | Walentin, K., Hinze, C., Werth, M., Haase, N., Varma, S., Morell, R., Aue, A., Pötschke, E., Warburton, D., Qiu, A., Barasch, J., Purfürst, B., Dieterich, C., Popova, E., Bader, M., Dechend, R., Staff, A.C., Yurtdas, Z.Y., Kilic, E. and Schmidt-Ott, K.M. |
| Abstract: | Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in pre-eclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branching morphogenesis. Selective Grhl2 inactivation only in epiblast-derived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIP-seq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2(-/-) placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction. |
| Keywords: | Placenta Defects, Epithelial Differentiation, Epithelial Morphogenesis, Spint1, Basement Membrane Defects |
| Source: | Development |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Volume: | 142 |
| Number: | 6 |
| Page Range: | 1125-1136 |
| Date: | 15 March 2015 |
| Official Publication: | https://doi.org/10.1242/dev.113829 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
