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Title: Genomic identification of hunchback targets in the Drosophila central nervous system
Author: Carr, A. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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Hunchback (Hb) is a transcription factor that determines the earliest temporal identity in the developing central nervous system. I have used whole genome oligonucleotide microarrays to identify genes that change in response to ectopic expression of Hunchback in the CNS. Using the GAL4/UAS system I expressed Hb exclusively in the embryonic CNS. Expression profiling identified 1095 up-regulated and 1590 down-regulated genes in response to Hunchback. Many of these genes have known neural functions in Drosophila or in mammals. A number of these genes have been implicated in Parkinson, Alzheimer’s and other neural conditions. Gene ontology indicates that transcription and protein folding genes in particular are up-regulated by Hb. Genes involved in ubiquitination and phosphorylation are enriched in the down regulated genes. To identify which genes Hunchback regulates in neuroblasts, the embryonic neural stem cells, I developed transcription single cell neuroblast expression profiling. This approach identified 681 genes that appear to be regulated in response to Hb in neuroblasts. These include many genes not identified my expression profiling with whole embryos. One gene identified as a Hb target from the microarray studies was the translational regulator Lin-28. Within the embryonic CNS, Lin-28 is virtually exclusively expressed with the first born ganglion mother cells, under the control of the transcription factors Hunchback and Prospero. Lin-28 mutants exhibit phenotypes in both the PNS and CNS. In the PNS, lin-28 mutant causes bristle duplication in the anterior scutellar bristles and leads to a reduction in the interocellular bristles. Ectopic expression of Lin-28 in the wing disc, phenocopies the bristle duplication phenotype and induces novel ectopic bristles on the wing. Affinity purification of mRNAs that bind to Lin-28 identifies translation factors and the Notch signalling pathway genes, m4 and mα.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available