Kaschula, Richard (2014) The regulation of Hox genes by microRNAs during Drosophila development. Doctoral thesis (PhD), University of Sussex.

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Abstract

Hox genes encode a family of evolutionarily conserved transcription factors involved in
the activation of diverse cell differentiation programs along the antero-posterior axis of
animals. Hox gene expression is controlled by a complex set of regulatory mechanisms
which are still not fully understood. Despite this, misregulation of Hox gene expression
can lead to severe developmental abnormalities and various forms of disease.
This work addresses the way in which small non-coding RNAs (microRNAs, miRNAs)
regulate Hox gene expression and function during development. To do this we use the
Drosophila Hox gene Ultrabithorax (Ubx) as a paradigm for Hox gene function.
Using a suite of genetic methods we first uncover a novel regulatory interaction
between Drosophila Ubx and the miR-310C family of miRNAs during the development
of the haltere, a small dorsal appendage involved in flight control. We also show that
this miRNA cluster is required to fine tune Ubx expression. Furthermore, our data
provides insight into the role played by Ubx during appendage development.
Secondly, using a next generation RNA sequencing approach, we identify the full
repertoire of miRNAs present in two serially homologous appendages of Drosophila –
the wing and haltere. Our results show that these morphologically distinct appendages
have divergent miRNA profiles, including miRNAs which display appendage-specific
expression patterns. In addition, combining these profiles with available transcriptomic
data enabled us to study how miRNAs are integrated into the Ubx gene regulatory
networks that govern haltere development. This analysis suggests that haltere miRNAs
reinforce the regulatory programmes installed by Ubx during haltere development.
Our work therefore contributes to the understanding of the regulatory function of
miRNAs during development and sheds light on the ways in which Hox gene
expression can contribute to the formation of complex morphological structures.

Item Type:	Thesis (Doctoral)
Schools and Departments:	School of Life Sciences > Biology and Environmental Science
Subjects:	Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome Q Science > QH Natural history > QH0301 Biology
Depositing User:	Library Cataloguing
Date Deposited:	30 May 2014 11:50
Last Modified:	30 May 2017 10:19
URI:	http://srodev.sussex.ac.uk/id/eprint/48805

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