School of Medicine and Health Sciences Poster Presentations
Hectd1 Promotes Retinoic Acid Signaling in the Epicardium Required for Myocardial Proliferation During Heart Development
Document Type
Poster
Keywords
Hectd1; Retinoic Acid; Heart Development; Myocardial Proliferation
Publication Date
Spring 2017
Abstract
Congenital heart defects (CHDs) are the most common structural birth defects in the United States. During heart development of the murine heart, epicardium expresses signaling factors that increase proliferation and differentiation of the adjacent myocardium. Disruptions in this communication may lead to hypoplastic ventricle phenotypes. One of the main signaling factors involved is retinoic acid (RA). Deficient levels of retinoic acid are associated with hypoplastic and thin-walled ventricles. Previous work demonstrates that the novel E3 ubiquitin-protein ligase Hectd1 promotes RA signaling. Hectd1 is highly expressed in the epicardium and mutation of Hectd1 results in defects in myocardial proliferation that resembles those seen in mice with defects in retinoic acid signaling. However, in addition to CHDs, Hectd1 mutant embryos exhibit a number of developmental phenotypes including neural tube closure and placental defects, which may indirectly influence heart development. To determine if CHDs are due to a role of Hectd1 in the heart, we utilized the Cre-lox system to specifically delete Hectd1 in cardiac lineages. Hectd1 was conditionally knocked out in mesodermal-derived cells, using Cre expressed under the control of Mesp1 and Nkx2.5 promoters. Mesp1-Cre is expressed throughout mesoderm-derived cell lines in the embryo and Nkx2.5-Cre is expressed in mesoderm-derived cardiac tissue. Our results show that Hectd1 is required in the mesodermal heart lineage for myocardial development. Future experiments will determine if Hectd1 in the epicardium using Wt1-Cre.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Open Access
1
Hectd1 Promotes Retinoic Acid Signaling in the Epicardium Required for Myocardial Proliferation During Heart Development
Congenital heart defects (CHDs) are the most common structural birth defects in the United States. During heart development of the murine heart, epicardium expresses signaling factors that increase proliferation and differentiation of the adjacent myocardium. Disruptions in this communication may lead to hypoplastic ventricle phenotypes. One of the main signaling factors involved is retinoic acid (RA). Deficient levels of retinoic acid are associated with hypoplastic and thin-walled ventricles. Previous work demonstrates that the novel E3 ubiquitin-protein ligase Hectd1 promotes RA signaling. Hectd1 is highly expressed in the epicardium and mutation of Hectd1 results in defects in myocardial proliferation that resembles those seen in mice with defects in retinoic acid signaling. However, in addition to CHDs, Hectd1 mutant embryos exhibit a number of developmental phenotypes including neural tube closure and placental defects, which may indirectly influence heart development. To determine if CHDs are due to a role of Hectd1 in the heart, we utilized the Cre-lox system to specifically delete Hectd1 in cardiac lineages. Hectd1 was conditionally knocked out in mesodermal-derived cells, using Cre expressed under the control of Mesp1 and Nkx2.5 promoters. Mesp1-Cre is expressed throughout mesoderm-derived cell lines in the embryo and Nkx2.5-Cre is expressed in mesoderm-derived cardiac tissue. Our results show that Hectd1 is required in the mesodermal heart lineage for myocardial development. Future experiments will determine if Hectd1 in the epicardium using Wt1-Cre.
Comments
Poster to be presented at GW Annual Research Days 2017.