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020 ▼a 9781085634922
035 ▼a (MiAaPQ)AAI13881363
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 574
1001 ▼a Grant, Meagan Geraldine.
24510 ▼a Interrogating The Roles of Signaling Cues During Asymmetric Morphogenesis of The Zebrafish Heart.
260 ▼a [S.l.]: ▼b Princeton University., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 70 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
500 ▼a Advisor: Burdine, Rebecca D.
5021 ▼a Thesis (Ph.D.)--Princeton University, 2019.
506 ▼a This item must not be sold to any third party vendors.
506 ▼a This item must not be added to any third party search indexes.
520 ▼a Vertebrate heart development is driven by an intricate succession of morphogenetic cell movements, the coordination of which requires precise interpretation of signaling cues by heart primordia. Failure to undergo any of the cellular and tissue-level events mediated by signaling molecules results in congenital heart defects, which affect 40,000 American infants each year. Thus, dissecting the links between signaling cues and the cellular movements that control heart development is crucial for understanding the pathogenic mechanism of these malformations.In zebrafish, the Nodal pathway governs directional cardiac precursor cell (CPC) migration by inducing left-right asymmetries in migration speeds. However, the molecular mechanisms through which this occurs are unknown, and the signals acting in concert with Nodal during this process have not been fully elucidated. Here, using two-photon imaging, we show that Nodal controls CPC migration by inducing left-right asymmetries in the formation of actin-based protrusions in CPCs. We further find that Nodal functions cooperatively with, and independently of, FGF signals during heart tube formation: both pathways act as migratory stimuli for CPCs, but FGF is dispensable for directing heart tube asymmetry, which is governed by the sidedness of Nodal expression in the lateral plate mesoderm. Moreover, aberrant Nodal and FGF signaling perturb the morphogenetic movements underpinning heart tube formation. We also interrogate the roles of Nodal and FGF signals during cardiac looping and chamber expansion: while both signals are required for proper looping chirality, only FGF signals are required for chamber expansion. Together, our data shed insight into how the spatio-temporal dynamics of signaling cues regulate the cellular behaviors underlying organ morphogenesis.
590 ▼a School code: 0181.
650 4 ▼a Molecular biology.
650 4 ▼a Physiology.
650 4 ▼a Public health.
650 4 ▼a Neurosciences.
650 4 ▼a Health sciences.
650 4 ▼a Developmental biology.
690 ▼a 0307
690 ▼a 0566
690 ▼a 0317
690 ▼a 0758
690 ▼a 0573
690 ▼a 0719
71020 ▼a Princeton University. ▼b Molecular Biology.
7730 ▼t Dissertations Abstracts International ▼g 81-03B.
773 ▼t Dissertation Abstract International
790 ▼a 0181
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15491184 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1816162
991 ▼a E-BOOK