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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 526 - 531 (6page)
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The vertebrate body plan is accomplished by left-right asymmetric organ development and the heart is a representative asymmetric internal organ which jogs to the left-side. Kupffer’s vesicle (KV) is a spherical left-right organizer during zebrafish embryogenesis and is derived from a cluster of dorsal forerunner cells (DFCs). Cadherin1 is required for collective migration of a DFC cluster and failure of DFC collective migration by Cadherin1 decrement causes KV malformation which results in defective heart laterality. Recently, loss of function mutation of A-kinase anchoring protein 12 (AKAP12) is reported as a high-risk gene in congenital heart disease patients. In this study, we demonstrated the role of akap12 in asymmetric heart development. The akap12, one of the akap12 isoforms, was expressed in DFCs which give rise to KV and akap12- deficient zebrafish embryos showed defective heart laterality due to the fragmentation of DFC clusters which resulted in KV malformation. DFC-specific loss of akap12 also led to defective heart laterality as a consequence of the failure of collective migration by cadherin1 reduction. Exogenous akap12 mRNA not only restored the defective heart laterality but also increased cadherin1 expression in akap12 morphant zebrafish embryos. Taken together, these findings provide the first experimental evidence that akap12 regulates heart laterality via cadherin1.
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참고문헌 (29)
참고문헌 신청
Essner JJ / 2005 / Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut / Development 132:1247~1260
Matsui T / 2011 / Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis / Proc Natl Acad Sci U S A 108:9881~9886
Oteiza P / 2008 / Origin and shaping of the laterality organ in zebrafish / Development 135:2807~2813
Desgrange A / 2018 / Left-right asymmetry in heart development and disease:forming the right loop / Development 145
van der Linde D / 2011 / Birth prevalence of congenital heart disease worldwide : a systematic review and meta-analysis / J Am Coll Cardiol 58:2241~2247
Matsui T / 2011 / Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis / Proc Natl Acad Sci U S A 108:9881~9886
Oteiza P / 2008 / Origin and shaping of the laterality organ in zebrafish / Development 135:2807~2813
Desgrange A / 2018 / Left-right asymmetry in heart development and disease:forming the right loop / Development 145
van der Linde D / 2011 / Birth prevalence of congenital heart disease worldwide : a systematic review and meta-analysis / J Am Coll Cardiol 58:2241~2247
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