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Title: Intersections between Notch signalling and planar polarity
Author: Johnson, R. I.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2003
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Planar polarity refers to the organisation of cells within the plane of the epithelium. In the Drosophila eye this is manifest in the chirality of the asymmetrical ommatidia determined by the specification of the R4 photoreceptor, and by the direction in which the ommatidia rotate during development. Genes involved in conferring appropriate planar polarity include frizzled and dishevelled. Frizzled is required in the R3/R4 photoreceptor precursors for ommatidia to correctly interpret polarity and mutations in frizzled and dishevelled subsequently affect the allocation of the R3 and R4 fates because Notch signalling, which is required to specify the R4 fate, is aberrant. The role that several genes implicated in planar polarity have in regulating Notch activity in this fate decision has been investigated using the Notch responsive enhancer md0.5 as an assay. One widely accepted model proposes that the Rac/Rho GTPases, the STE-20 like kinase Misshapen, and components of the JNK cascade transduce a polarity signal downstream of Frizzled to upregulate transcription of the Notch ligand Delta. Evidence presented here indicates that these factors are not essential to regulate Notch activity in this tissue and that regulation of the ligands is not critical for introducing a bias in Notch activity in this cell fate. An alternative model is proposed in which asymmetrical localisation of several core polarity proteins results in asymmetrical activation of N across the R3/R4 cell boundary. This is based on the observation that a number of genes are essential for normal Notch signalling. Frizzled is required in the R3 precursor and localises to the membrane abutting the R4 cell at the time when Notch activity between these cells is resolved in an equatorial to polar direction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available