Role of the nodal signaling pathway in left-right morphogenesis of the zebrafis...

• Author(s): Baptista, Maria Inês Medeiros de Campos, 1978-
• Date: 2009
• Persistent ID: http://hdl.handle.net/10451/1615
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Peixe-zebra; Coração; Assimetria; Morfogenese; Teses de doutoramento - 2009
• Document Type: Doctoral Thesis
• Language: Portuguese
• Advisor(s): Thorsteinsdóttir, Sólveig, 1962-

Description

Although externally bilaterally symmetric, vertebrates display asymmetry in the way their internal organs are shaped and distributed within the body cavity. The Nodal signaling pathway has long been implicated in the establishment of left right asymmetry in vertebrates. Nodals are members of the TGF ß super family that signal to the interior of the cell to activate downstream targets, such as Nodal itself and lefty2, a pathway inhibitor. Many of the genes in the Nodal signaling pathway have a conserved asymmetric expression pattern in the left lateral plate mesoderm (LPM). Little is known on how this asymmetric gene expression translates into asymmetric morphogenesis. To address this question I studied the process of asymmetry acquisition in the zebrafish heart. The heart is the first organ to form and function in vertebrates. Initially, the bilateral fields of cardiomyocytes on the left and right LPM migrate toward the midline to fuse and form the heart cone, a symmetric ring shaped structure centered in a lumen. The cone tilts and extends to form the heart tube. During heart tube formation symmetry is broken and the cardiac structure develops toward the left of the embryo. The Nodal gene southpaw is expressed adjacently to the cardiomyocytes, whereas lefty2 is expressed in the left side of the heart. In this thesis I analyzed how Nodal expression instructs cells to break organ symmetry. Studies on embryos lacking Nodal signaling (LZoep mutants) revealed that Nodal promotes the speed and directional movement of cardiomyocytes (Chapter II). Analyses of embryos with bilateral Nodal expression (ntl morphants) or Nodal expressed solely in the right LPM (polaris morphants) confirmed and extended these results (Chapter III). Preliminary results suggest that asymmetry initiates with a leftward displacement of the lumen (Chapter IV). Taken together, my results indicate that asymmetric Nodal signaling regulates the speed and guides the movement of heart cells and thus establishes left right asymmetry during organogenesis Tese de doutoramento, Biologia (Biologia do Desenvolvimento), Universidade de Lisboa, Faculdade de Ciências, 2009 Fundação para a Ciência e a Tecnologia (SFRH/BD/11801/2003) e NIH grant R01 GM56211