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Essential Roles of Convergence and Extension Gastrulation Movements in Zebrafish Somite Development

dc.creatorYin, Chunyue
dc.date.accessioned2020-08-21T21:01:42Z
dc.date.available2008-02-27
dc.date.issued2007-02-27
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-02152007-100239
dc.identifier.urihttp://hdl.handle.net/1803/10572
dc.description.abstractDuring vertebrate gastrulation, massive cell movements shape the basic body plan. Key components of gastrulation are convergence and extension (C&E) movements, which narrow and lengthen the embryonic tissues, respectively. By studying knypek;trilobite non-canonical Wnt mutants with impaired C&E, I demonstrate crucial roles of C&E gastrulation movements in multiple aspects of zebrafish somite development. Combining time-lapse analyses and computational simulations, I show that C&E movements of the medial presomitic mesoderm are achieved by the cooperation of planar and radial cell intercalations that preferentially separate anterior and posterior neighbors. In knypek;trilobite double mutants, the anteroposterior bias of cell intercalations is reduced and the asymmetric localization of non-canonical Wnt components is lost, revealing that non-canonical Wnt signaling defines distinct properties of anterior and posterior cell edges to bias the orientation of cell intercalation. Using cell tracing analyses and genetic manipulations, I demonstrate that C&E mediates the specification and fate maintenance of slow muscle precursors, the adaxial cells. During gastrulation, C&E regulates the number of specified adaxial cells by defining the size of the interface between the inducing axial and target presomitic tissues. After somite forms, convergence movements ensure the tight apposition of adaxial cells to the notochord, which is necessary for their continuous Hedgehog reception and fate maintenance. I further demonstrate that in knypek;trilobite double mutants, impaired C&E disrupts notochord development, which in turn impedes the adaxial cell shape changes and interferes with their lateral migration during later somitogenesis. Additionally, in a genetic screen for genes essential for zebrafish early development, we isolated the calamityvu69 mutation that affects pigmentation and notochord development. We determined that calamityvu69 inactivates a zebrafish homolog of the human Menkes atp7a gene, which is critical for copper homeostasis in humans. Genetic mosaic analyses indicate that atp7a acts cell-autonomously in melanocytes to ensure melanin synthesis. Identification of the calamityvu69 mutant establishes a novel vertebrate model for studying the human Menkes disease and copper metabolism.
dc.format.mimetypeapplication/pdf
dc.subjectmenkes disease
dc.subjectcopper
dc.subjectcalamity
dc.subjectnon-canonical Wnt signaling
dc.subjectknypek
dc.subjecttrilobite
dc.subjectplanar cell polarity
dc.subjectslow muscle
dc.subjectadaxial cell
dc.subjectintercalation
dc.subjectmodeling
dc.subjectspecification
dc.subjectmorphogenesis
dc.subjectHypocupremia
dc.subjectZebra danio -- Embryology
dc.subjectGastrulation
dc.titleEssential Roles of Convergence and Extension Gastrulation Movements in Zebrafish Somite Development
dc.typedissertation
dc.contributor.committeeMemberLilianna Solnica-Krezel
dc.contributor.committeeMemberBruce Appel
dc.contributor.committeeMemberChristopher V.E. Wright
dc.contributor.committeeMemberChin Chiang
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineBiological Sciences
thesis.degree.grantorVanderbilt University
local.embargo.terms2008-02-27
local.embargo.lift2008-02-27
dc.contributor.committeeChairTodd R. Graham


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