The role of Wnt signalling during embryonic salivary gland development

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

A universally conserved process called branching morphogenesis generates the final tree-like structure that is a characteristic of the salivary glands and other organs including the lungs, kidneys and mammary glands. Branching morphogenesis is the mechanism by which a single epithelial bud undergoes repetitive cycles of bifurcation in order to maximise its surface area within a confined space. During salivary gland development, alongside branching morphogenesis occurs lumen formation, which corresponds to the cavitation of the inside of the epithelial branches to form ducts. Branching and canalization take place in a controlled manner, so that branching is active at the distal ends of epithelial branches while lumen formation initiates at the proximal ends, and spreads distally. We looked at the function of Wnt signaling during embryonic development of the submandibular and sublingual salivary glands and found that FGF signaling acts upstream of Wnt signaling and that Wnt and FGF signals coordinate branching morphogenesis and lumen formation. To locate the sites of active Wnt/p-catenin signaling, we used Axin2LacZ mice and found that the pathway is active from early stages of salivary gland development in the mesenchyme and at later stages in the ductal epithelium corresponding to the time of branching morphogenesis and lumen formation, respectively. The use of an array of ex vivo gain and loss of function experiments revealed that Wnt/b-catenin signaling exerts an inhibitory effect on branching morphogenesis and that tight regulation of this pathway is critical for correct salivary gland development. We also present data showing critical interactions between the Wnt and FGF signaling pathways, whereby the endbuds remain devoid of Wnt/p-catenin signaling, a hallmark of ductal structures, through FGF mediated inhibition of this pathway.

Snippet: and mammary glands. Branching morphogenesis is the mechanism by which a single epithelial bud undergoes repetitive cycles of bifurcation in order to maximise its surface area within a confined space... canalization take place in a controlled manner, so that branching is active at the distal ends of epithelial branches while lumen formation initiates at the proximal ends, and spreads distally. We looked... A universally conserved process called branching morphogenesis generates the final tree-like structure that is a characteristic of the salivary glands and other organs including the lungs, kidneys... . During salivary gland development, alongside branching morphogenesis occurs lumen formation, which corresponds to the cavitation of the inside of the epithelial branches to form ducts. Branching and... at the function of Wnt signaling during embryonic development of the submandibular and sublingual salivary glands and found that FGF signaling acts upstream of Wnt signaling and that Wnt and FGF... The role of Wnt signalling during embryonic salivary gland development /
Date of Award2011
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorIsabelle Miletich (Supervisor)

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