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Title: Elucidating the molecular mechanisms underlying cell movements during early embryogenesis
Author: Joyce, Bradley
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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The anterior visceral endoderm (AVE) is a specialised subpopulation of the visceral endoderm (VE), a single layer simple epithelium that surrounds the extra-embryonic ectoderm and epiblast of the egg cylinder stage embryo. Initially induced at the distal tip of the egg cylinder, AVE cells undergo a stereotypic migration towards the prospective anterior, stopping at the interface between the underlying epiblast and extra-embryonic ectoderm (ExE). Previous research has shown that membrane enrichment of Dvl2 is present in the VE overlying the epiblast (Epi-VE). In this thesis I confirm the presence of planar cell polarity (pep) signalling in this region by assaying the subcellular localisation of additional core pep proteins Vangl2 and Daaml. I show that null embryos of the Nodal antagonist Lefty1 exhibit ectopic membrane enrichment of Dvl2 and a previously unreported AVE over-migration phenotype. Furthermore, using pharmacological inhibition of Nodal signalling I show that the TGF~ protein Nodal modulates pep signalling in the YE. Utilising DIe and confocal microscopy I perform detailed time-lapse analyses of the VE to quantify the dynamic cell behaviour and topology. Using this assay I show that wild-type embryos exhibit dynamic cell movement, which is regionally restricted to the Epi-VE. Analysis of Leftyl-/- and ROSA26lyn-Celsr-l mutants, both of which exhibit disrupted pep signalling and AVE over-migration phenotypes, indicates that normal VE dynamics and topology are disrupted. The results of this quantitation indicate that these mutants exhibit increased cell migration and neighbour exchange across the YE. These data show that regional restriction of movement is lost and results in the AVE over-migration phenotypes observed. Together these results show that regionally restricted pep signalling in the VE acts to modulate cell behaviour and topology, which in turn determines the regional restriction and normal end-point of AVE migration.
Supervisor: Srinivas, Shankar Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Embryology ; Mice--Embryology ; Cell migration