TIMING CELL DIFFERENTIATON: Gene Regulatory Network in Temporal Control of Mesoderm Specification

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Organizational Unit

Publications

Novel dynamics and functions of Fibronectin in early vertebrate development

Publication . Gomes De Almeida, Patrícia; Thorsteinsdóttir, Sólveig; Palmeirim, Isabel; Andrade, Raquel P.

The metameric body plan of vertebrates is established during somitogenesis, one of the most complex morphogenetic events during development. Somites epithelialize periodically from the anterior-most presomitic mesoderm, and this rhythmicity is thought to be controlled by cyclic traveling waves of gene expression that sweep the tissue anteriorly. Although the spatial and temporal regulation of somitogenesis has been extensively studied, how the periodicity of genetic oscillations is translated into periodic somite epithelialization remains elusive. Furthermore, while knockout experiments have implicated the extracellular matrix component fibronectin in somite formation, much of the roles of its qualitative features deriving from its assembly state are still unknown. The aim of this thesis is to re-address the role of fibronectin during paraxial mesoderm development, particularly during somite morphogenesis. In Chapter 2, we describe fibronectin production and assembly dynamics during early embryogenesis and found that it is highly dynamic throughout paraxial mesoderm development, as different forms of fibronectin assembly (autocrine vs paracrine) correlate with exquisite morphogenetic events. In Chapter 3 we re-address the role of fibronectin during somite formation in vivo. We show that an intact fibronectin matrix and downstream mechanotransduction signaling are required for correct segmentation clock dynamics and somite morphogenesis. Our results suggest that the fibronectin matrix and its downstream chemical and mechanical cues couple genetic oscillations with timely somite morphogenesis. In Chapter 4 we investigate the role of fibronectin in somite maturation. We demonstrate that normal fibronectin assembly is required for correct Sonic hedgehog signaling in the somite, which in turn controls fibronectin production in this tissue, suggesting that fibronectin and Sonic cooperate to orchestrate somite patterning and differentiation. This thesis demonstrates that fibronectin is a dynamic pivotal player regulating paraxial mesoderm development. It also highlights the previously unappreciated importance of the extracellular matrix and its derived mechanical cues during embryonic development.

2019-02Doctoral thesis

Open access