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Title: Role of Wnt signalling in forebrain development
Author: McLaughlin, David Anthony
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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In situ hybridisation (ISH) was used to determine the expression pattern of a new member of the Wnt gene family Wnt8B. During early development Wnt8B expression was observed in the cerebral cortical hem region which is presumptive for the hippocampus. In the adult, Wnt8B is expressed in the dentate gyrus region of the hippocampus, one of the areas in which adult neurogenesis takes place. To investigate the role of Wnt8B in regulating central nervous system development we undertook histological analysis and 5-bromo2-deozyuridine (BrdU) studies in Wnt8B+/+ and Wnt8B-/- mice in regions where Wnt8B is expressed. Surprisingly, histological analysis showed no obvious abnormalities in Wnt8B-/- animals. Further, no significant differences in cell proliferation were found in BrdU studies in the Wnt8B-/- embryos or adult mice. Heparan sulphate proteoglycans are structurally dynamic molecules required for Wnt signalling. The nature of specific structural modifications made to these molecules such as the sulphation pattern is thought to confer specific biological effects. To determine the role of 2-0 sulphation in cellular proliferation in the cerebral cortical hem during development, BrdU studies were undertaken in mice deficient in the enzyme heparan sulphate 2-0 sulphotransferase (Hs2st). BrdU labelling was also used to investigate cell migration in the cerebral cortex and a combination of histochemical techniques was applied to look for gross and subtle anatomical defects in the forebrain of Hs2st-/- mice. In agreement with a dramatically reduced thickness of the cerebral cortex seen in histological sections, BrdU labelling indicated proliferative rates 40% lower in Hs2st-/- mice. Finally, the developmental expression of a member of the Wnt gene receptor family Frizzled-1 was examined using in situ hybridisation with particular emphasis on co-expression with Wnt10B. Frizzled-1 expression was found in the developing tooth, limb and forebrain which coincided with expression of Wnt10B suggesting a possible ligand-receptor relationship.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available