Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation
MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during earl...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.767954/full |
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| author | Carlos Garcia-Padilla Carlos Garcia-Padilla Angel Dueñas Angel Dueñas Diego Franco Diego Franco Virginio Garcia-Lopez Amelia Aranega Amelia Aranega Virginio Garcia-Martinez Carmen Lopez-Sanchez |
| author_facet | Carlos Garcia-Padilla Carlos Garcia-Padilla Angel Dueñas Angel Dueñas Diego Franco Diego Franco Virginio Garcia-Lopez Amelia Aranega Amelia Aranega Virginio Garcia-Martinez Carmen Lopez-Sanchez |
| author_sort | Carlos Garcia-Padilla |
| collection | DOAJ |
| description | MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart. |
| first_indexed | 2024-12-20T07:26:14Z |
| format | Article |
| id | doaj.art-fca728c2040a4a71a45460d4ff44ea6e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-20T07:26:14Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-fca728c2040a4a71a45460d4ff44ea6e2022-12-21T19:48:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.767954767954Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract DifferentiationCarlos Garcia-Padilla0Carlos Garcia-Padilla1Angel Dueñas2Angel Dueñas3Diego Franco4Diego Franco5Virginio Garcia-Lopez6Amelia Aranega7Amelia Aranega8Virginio Garcia-Martinez9Carmen Lopez-Sanchez10Department of Human Anatomy and Embryology, Faculty of Medicine, Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, SpainDepartment of Experimental Biology, University of Jaen, Jaen, SpainDepartment of Human Anatomy and Embryology, Faculty of Medicine, Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, SpainDepartment of Experimental Biology, University of Jaen, Jaen, SpainDepartment of Experimental Biology, University of Jaen, Jaen, SpainFundación Medina, Granada, SpainDepartment of Human Anatomy and Embryology, Faculty of Medicine, Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, SpainDepartment of Experimental Biology, University of Jaen, Jaen, SpainFundación Medina, Granada, SpainDepartment of Human Anatomy and Embryology, Faculty of Medicine, Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, SpainDepartment of Human Anatomy and Embryology, Faculty of Medicine, Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, SpainMicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart.https://www.frontiersin.org/articles/10.3389/fcell.2021.767954/fullheart developmentmicroRNAsexpression profilesHox genessinus venosusinflow tract |
| spellingShingle | Carlos Garcia-Padilla Carlos Garcia-Padilla Angel Dueñas Angel Dueñas Diego Franco Diego Franco Virginio Garcia-Lopez Amelia Aranega Amelia Aranega Virginio Garcia-Martinez Carmen Lopez-Sanchez Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation Frontiers in Cell and Developmental Biology heart development microRNAs expression profiles Hox genes sinus venosus inflow tract |
| title | Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation |
| title_full | Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation |
| title_fullStr | Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation |
| title_full_unstemmed | Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation |
| title_short | Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation |
| title_sort | dynamic microrna expression profiles during embryonic development provide novel insights into cardiac sinus venosus inflow tract differentiation |
| topic | heart development microRNAs expression profiles Hox genes sinus venosus inflow tract |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.767954/full |
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