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Title: Notch targets in the Drosophila hematopoietic system
Author: Collins, S. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Expression arrays and chromatin immunoprecipitation in a Drosophila blood cell line had previously identified high confidence direct targets of Notch signalling. Therefore one aim of the research was to validate a selection of these putative Notch targets. These were shown to contain Notch responsive enhancers that direct expression in the lymph gland, implicating these novel targets in blood cell regulation. Further analysis of two of these novel Notch targets, hindsight (hnt) and klumpfuss (klu) indicate that their expression overlaps with a known crystal cell-lineage marker, lozenge (lz). This suggests that these, and most likely the other targets, are involved downstream of Notch in precursor cells during crystal cell specification, as part of the gene cascade that results in terminal differentiation. My work has found that hnt and klu are both necessary for crystal differentiation, acting downstream of Notch and Lz. Furthermore, klu is sufficient to induce crystal cell fates in cells of another lineage. My work further suggests that Notch and Lz act in a co-ordinate manner. The model that emerges is that expression of lz confers competence to receive the Notch signal, so that the receiving cells activate genes required to promote crystal cell differentiation, including hnt and klu. The requirement of Notch and Lz in Drosophila hematopoiesis echo that of NOTCH1 and the homologue of Lz, Runx1, in the mammalian system, suggesting that novel targets identified here may be relevant to the regulatory networks involved in mammals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available