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Title: Analysis of neural development using ligand-trap transgenic lines
Author: Milne, Charlotte Anne
ISNI:       0000 0004 2674 4665
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2007
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Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor-beta (TGF-beta) signalling protein superfamily. BMPs play important and diverse roles in cell-cell signalling, including establishing cell fate during the development of vertebrate embryos. Their activity is antagonised in vivo by a number of proteins such as noggin, which sequester BMP ligands, preventing them from binding to BMP receptors. This thesis describes studies to establish a binary genetic approach combined with a ligand trap system to manipulate BMP signalling in the frog embryo. This system has been used to investigate the roles of BMP signalling in dorso-ventral patterning of the forebrain Xenopus tropicalis. The binary system described utilises a variety of tissue- or region-specific gene promoters to drive expression of the GAL4 transcriptional activator. Such transgenic "driver" lines can be crossed with a "responder" line in which expression of a membrane-tethered fusion protein comprising human Noggin fused to GFP is regulated by a synthetic promoter responsive to GAL4 (UAS-flognog). Transient expression assays confirmed the effectiveness of the "responder" line, GAL4 transactivation of UAS-flognog resulted in the expression of Flognog and an expansion of neural progenitor tissue, indicated by the X-Sox3 marker. In a binary cross with the Otx2-gal4 driver line, targeted GAL4 transactivation lead to a decrease in phospho-Smad-1 staining in the anterior CNS and eye in a proportion of cross embryos. Such a cross resulted in embryos showing an open neural tube and alterations in both Pax6 (dorsal) and X-
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available