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Mechanisms of Heart and Major Vessel Development: Nup107 and Cacna1g As Novel Regulators
Mechanisms of Heart and Major Vessel Development: Nup107 and Cacna1g As Novel Regulators
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202102957
- ISBN
- 9798286444045
- DDC
- 574
- 서명/저자
- Mechanisms of Heart and Major Vessel Development: Nup107 and Cacna1g As Novel Regulators
- 발행사항
- [Sl] : Yale University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 121 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Nitabach, Michael;Khokha, Mustafa K.
- 학위논문주기
- Thesis (Ph.D.)--Yale University, 2025.
- 초록/해제
- 요약Congenital Heart Disease (CHD) is the most common congenital malformation and a leading cause of infant mortality. While advances in genomic sequencing technology have enabled a fast and inexpensive candidate gene identification, the molecular mechanisms of CHD remain mostly unknown. Both nup107 and cacna1g are novel CHD genes identified in CHD patients with no plausible mechanisms explaining their roles in cardiac development. Here, we show that nup107 plays a key role in early embryonic patterning and subsequent organ development. The loss of Nup107 has a direct impact on germ layer specification, Left-Right patterning and downstream cardiac looping. Specifically, Nup107 depletion affects multiple developmental events by regulating the key step during the maternal-zygotic transition. In particular, Nup107 enhances the nuclear retention of miR427 primary transcript (pri-miR427), where it can be processed by Drosha to facilitate the clearance of maternal transcripts. While cacna1g mutations were also found in patients with CHD, we show that Cacna1g affects organogenesis via a completely distinct mechanism. Specifically, our results indicate that cacna1g loss-of-function affects Left-Right patterning and subsequent cardiac development by reducing the number of cilia in the Left-Right Organizer. In summary, we describe two mechanisms of how novel candidate genes affect different stages of embryonic development and contribute to CHD.
- 일반주제명
- Developmental biology
- 일반주제명
- Medicine
- 일반주제명
- Molecular biology
- 키워드
- Infant mortality
- 기타저자
- Yale University Genetics
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798286444045
■035 ▼a(MiAaPQ)AAI31770321
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aKostiuk, Valentyna.
■24510▼aMechanisms of Heart and Major Vessel Development: Nup107 and Cacna1g As Novel Regulators
■260 ▼a[Sl]▼bYale University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a121 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Nitabach, Michael;Khokha, Mustafa K.
■5021 ▼aThesis (Ph.D.)--Yale University, 2025.
■520 ▼aCongenital Heart Disease (CHD) is the most common congenital malformation and a leading cause of infant mortality. While advances in genomic sequencing technology have enabled a fast and inexpensive candidate gene identification, the molecular mechanisms of CHD remain mostly unknown. Both nup107 and cacna1g are novel CHD genes identified in CHD patients with no plausible mechanisms explaining their roles in cardiac development. Here, we show that nup107 plays a key role in early embryonic patterning and subsequent organ development. The loss of Nup107 has a direct impact on germ layer specification, Left-Right patterning and downstream cardiac looping. Specifically, Nup107 depletion affects multiple developmental events by regulating the key step during the maternal-zygotic transition. In particular, Nup107 enhances the nuclear retention of miR427 primary transcript (pri-miR427), where it can be processed by Drosha to facilitate the clearance of maternal transcripts. While cacna1g mutations were also found in patients with CHD, we show that Cacna1g affects organogenesis via a completely distinct mechanism. Specifically, our results indicate that cacna1g loss-of-function affects Left-Right patterning and subsequent cardiac development by reducing the number of cilia in the Left-Right Organizer. In summary, we describe two mechanisms of how novel candidate genes affect different stages of embryonic development and contribute to CHD.
■590 ▼aSchool code: 0265.
■650 4▼aDevelopmental biology
■650 4▼aMedicine
■650 4▼aMolecular biology
■653 ▼aCongenital Heart Disease
■653 ▼aCongenital malformation
■653 ▼aInfant mortality
■653 ▼aVessel development
■653 ▼aMolecular mechanisms
■690 ▼a0758
■690 ▼a0564
■690 ▼a0307
■690 ▼a0769
■71020▼aYale University▼bGenetics.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0265
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356584▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
