Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries
Background Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart proge...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-05-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1161/JAHA.115.001889 |
| _version_ | 1818032812785139712 |
|---|---|
| author | Mayu Narematsu Tatsuya Kamimura Toshiyuki Yamagishi Mitsuru Fukui Yuji Nakajima |
| author_facet | Mayu Narematsu Tatsuya Kamimura Toshiyuki Yamagishi Mitsuru Fukui Yuji Nakajima |
| author_sort | Mayu Narematsu |
| collection | DOAJ |
| description | Background Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart progenitors that originated from the left and right AHF migrate to form distinct conotruncal regions. The aim of this study is to identify abnormal AHF development that causes the morphology of transposition of the great arteries. Methods and Results We placed a retinoic acid–soaked bead on the left or the right or on both sides of the AHF of stage 12 to 14 chick embryos and examined the conotruncal heart defect at stage 34. Transposition of the great arteries was diagnosed at high incidence in embryos for which a retinoic acid–soaked bead had been placed in the left AHF at stage 12. Fluorescent dye tracing showed that AHF exposed to retinoic acid failed to contribute to conotruncus development. FGF8 and Isl1 expression were downregulated in retinoic acid–exposed AHF, and differentiation and expansion of cardiomyocytes were suppressed in cultured AHF in medium supplemented with retinoic acid. Conclusions The left AHF at the early looped heart stage, corresponding to Carnegie stages 10 to 11 (28 to 29 days after fertilization) in human embryos, is the region of the impediment that causes the morphology of transposition of the great arteries. |
| first_indexed | 2024-12-10T06:13:19Z |
| format | Article |
| id | doaj.art-31bf14df481848b5b86f12fae409bb8c |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-10T06:13:19Z |
| publishDate | 2015-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-31bf14df481848b5b86f12fae409bb8c2022-12-22T01:59:30ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802015-05-0145n/an/a10.1161/JAHA.115.001889Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great ArteriesMayu Narematsu0Tatsuya Kamimura1Toshiyuki Yamagishi2Mitsuru Fukui3Yuji Nakajima4Department of Anatomy and Cell Biology Graduate School of Medicine Osaka City University Osaka JapanDepartment of Anatomy and Cell Biology Graduate School of Medicine Osaka City University Osaka JapanDepartment of Anatomy and Cell Biology Graduate School of Medicine Osaka City University Osaka JapanLaboratory of Statics Graduate School of Medicine Osaka City University Osaka JapanDepartment of Anatomy and Cell Biology Graduate School of Medicine Osaka City University Osaka JapanBackground Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart progenitors that originated from the left and right AHF migrate to form distinct conotruncal regions. The aim of this study is to identify abnormal AHF development that causes the morphology of transposition of the great arteries. Methods and Results We placed a retinoic acid–soaked bead on the left or the right or on both sides of the AHF of stage 12 to 14 chick embryos and examined the conotruncal heart defect at stage 34. Transposition of the great arteries was diagnosed at high incidence in embryos for which a retinoic acid–soaked bead had been placed in the left AHF at stage 12. Fluorescent dye tracing showed that AHF exposed to retinoic acid failed to contribute to conotruncus development. FGF8 and Isl1 expression were downregulated in retinoic acid–exposed AHF, and differentiation and expansion of cardiomyocytes were suppressed in cultured AHF in medium supplemented with retinoic acid. Conclusions The left AHF at the early looped heart stage, corresponding to Carnegie stages 10 to 11 (28 to 29 days after fertilization) in human embryos, is the region of the impediment that causes the morphology of transposition of the great arteries.https://doi.org/10.1161/JAHA.115.001889congenitalheart defectsIsl1morphogenesistransposition of great vessel |
| spellingShingle | Mayu Narematsu Tatsuya Kamimura Toshiyuki Yamagishi Mitsuru Fukui Yuji Nakajima Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease congenital heart defects Isl1 morphogenesis transposition of great vessel |
| title | Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries |
| title_full | Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries |
| title_fullStr | Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries |
| title_full_unstemmed | Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries |
| title_short | Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries |
| title_sort | impaired development of left anterior heart field by ectopic retinoic acid causes transposition of the great arteries |
| topic | congenital heart defects Isl1 morphogenesis transposition of great vessel |
| url | https://doi.org/10.1161/JAHA.115.001889 |
| work_keys_str_mv | AT mayunarematsu impaireddevelopmentofleftanteriorheartfieldbyectopicretinoicacidcausestranspositionofthegreatarteries AT tatsuyakamimura impaireddevelopmentofleftanteriorheartfieldbyectopicretinoicacidcausestranspositionofthegreatarteries AT toshiyukiyamagishi impaireddevelopmentofleftanteriorheartfieldbyectopicretinoicacidcausestranspositionofthegreatarteries AT mitsurufukui impaireddevelopmentofleftanteriorheartfieldbyectopicretinoicacidcausestranspositionofthegreatarteries AT yujinakajima impaireddevelopmentofleftanteriorheartfieldbyectopicretinoicacidcausestranspositionofthegreatarteries |