Moverley, Adam A.; (2025) Imaging the cellular dynamics of morphogenesis: from early cleavage stages to embryogenesis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Throughout the history of developmental biology, the microscope has consistently proven one of the most powerful tools available to researchers. Here we use high resolution microscopy to probe cellular behaviours during tissue patterning, using the preimplantation mouse and chicken embryos as model systems. During preimplantation development the segregation of cells into inner and outer positions of the embryo is key to establishing the inner cell mass (ICM) and trophectoderm. Using the mouse embryo as a model, we found that the nuclear lamina links to the cell cortex via an F-actin meshwork, and Lamin-A levels are upregulated in response to actomyosin contractility. When cells internalise, cells lose their contractile apical cortex and Lamin-A is downregulated. This causes the localisation of Formin-2 to the cytoplasm and increases cytoplasmic F-actin. This, in turn stabilises Amot, causing Yap phosphorylation and acquisition of ICM identity. In outer cells, Lamin-A levels remain high, preventing Yap phosphorylation, leading to Cdx2 expression and trophectoderm identity. Later in development, the axis of the embryo is laid down in head-to-tail order. During this time, the somites form in pairs on either side of the midline. Somites are transient blocks of tissue that form as the mesenchymal cells of the presomitic mesoderm (PSM) undergo mesenchymal-to-epithelial transition (MET). Using scanning electron microscopy (SEM), immunofluorescence, and confocal microscopy we show that cells of the PSM undergo a gradual MET that begins earlier than previously reported. Epithelialisation began in the dorsal and medial PSM, progressing to the anterior and finally the lateral PSM. Inhibition of Notch signalling stops the oscillatory expression of clock genes but does not change epithelialisation dynamics in the PSM. Finally, live imaging was used to examine the relationship between cell cycle timing and segmentation and demonstrate the presence of a stem cell population in the posterior part of the node.

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