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Title page for ETD etd-02152007-100239


Type of Document Dissertation
Author Yin, Chunyue
URN etd-02152007-100239
Title Essential Roles of Convergence and Extension Gastrulation Movements in Zebrafish Somite Development
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Todd R. Graham Committee Chair
Bruce Appel Committee Member
Chin Chiang Committee Member
Christopher V.E. Wright Committee Member
Lilianna Solnica-Krezel Committee Member
Keywords
  • menkes disease
  • copper
  • calamity
  • non-canonical Wnt signaling
  • knypek
  • trilobite
  • planar cell polarity
  • slow muscle
  • adaxial cell
  • intercalation
  • modeling
  • specification
  • morphogenesis
  • Hypocupremia
  • Zebra danio -- Embryology
  • Gastrulation
Date of Defense 2007-01-26
Availability unrestricted
Abstract
During 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.

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