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Title: Investigation into the role of planar cell polarity in axis formation of the early mammalian embryo
Author: Crompton, Lucy Annabel
ISNI:       0000 0001 3397 167X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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In the early mammalian embryo cells undergo differentiation into specific lineages, which are assembled into a blueprint for the matwe body plan. This blueprint consists of is the three definitive embryonic axis, anteriorposterior, dorso-ventral and left-right. The first axis to be established is the anterior-posterior axis. Two critical events in anterior-posterior axis development are the induction and migration of the Anterior Visceral Endoderm (AVE) at 5.5 days post coitum (dpc) and gastrulation at 6.5 dpc. The AVE is a signaling centre.required for anterior specification. Gastrulation is the process that generates the three germ layers. Both AVE migration and gastrulation involve epithelial cells undergoing rearr.engement and directed cell movements, however the underlying molecular mechanisms that control these cell movements remain unknown. This thesis explores a possible role for the Planar Cell Polarity (PCP) pathway during anterior-posterior axis development. The PCP pathway is an evolutionarily conserved pathway, which in Drosophila regulates tissue polarity and cell movements primarily through modification of the cytoskeleton. A core group of PCP proteins have been defined including the membrane recep.tor Frizzled, the cytoplasmic proteins Dishevelled and Prickle, and the transmembrane proteins Flamingo and Strabismus. They co-localize to form asymmetric complexes within the cell, which modulate cytoskeletal components thus resulting in changes in cell shape or position, or arrangement of a whole tissue. This work focuses on the Prickle orthologues Prickle 1, Prickle2 and Testin, and the Flamingo orthologues Ge/sr1-3. In the first place the expression patterns of these Prickle and Ge/sr family members were characterised between 5.5 and 8.0 dpc. Given their expression in the AVE and gastrulating cells Testin and Ge/sr1 were chosen for functional analysis. To study the role of Testin during embryonic development two approaches have been taken. A genetrap mutation that generates a null Testin allele was analyzed. In addition genetic interaction experiments with another PCP orthologue, Vangl1, were carried out. To examine the role of Celsr1 in A-P axis formation an inqucible dominant negative Celsr1 mutation was generated. This thesis reports the analysis of these PCP pathway mutations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available