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Title: Control of longitudinal glial proliferation in the embryonic central nervous system of Drosophila
Author: Griffiths, R. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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Matching of neurons and glia is necessary for central nervous system development. I aimed to elucidate the pattern of longitudinal glial (LG) proliferation and its potential control by neurons. I characterised the LG cell lineage by wide-field and confocal microscopy using immunohistochemistry to monitor the distribution of phosphoHistone H3 ad Cyclins A, B and E. This lineage divides first into four and then six, finally resulting in nine to eleven glia. Neuronal ablation using the Ga14/UAS system resulted in an early reduction and a late increase in the proliferation of the subset of LG which express the gene prospero. Despite the symmetric cell divisions of the lineage wild-type and mutant analysis revealed that Miranda segregates Prospero and Numb asymmetrically during early LG divisions. The unequal distribution of Prospero segregates glial fate, causing the activation of the MAPKinase pathway by Vein in two of four glia, to coordinate glial cell division with axon guidance. In fact, prospero mutations also affect cell division. Normally the first divisions are rapid and the LG pause at four cells. At this point Prospero regulates Cyclin E introducing the first G1. Prospero regulates Notch in the LG and Notch also regulates Prospero in antagonism to Numb. This feed back loop results in the segregation of Prospero to a subset of six of the final LG. I show that the subset of six LG expressing Notch and prospero are arrested in G1 as opposed to G0. Target expression of cyclin E to the LG can only induce entry into S phase, monitored with BrdU, of the LG that express prospero. Non-Prospero longitudinal glia express dacapo triggering cell cycle exit and terminal differentiation. Ectopic Dacapo and Prospero demonstrate that these two proteins antagonise each other.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available