Pickering, Joseph (2012) The expression and regulation of lama1, a gene encoding Laminin alpha 1, during zebrafish development. PhD thesis, University of Sheffield.
Abstract
The Hedgehog (Hh) signalling pathway is one of the major signalling pathways governing embryonic and adult development in bilateria, yet many of the direct targets of Hh signalling remain unknown. Here, I use the zebrafish embryo to investigate two potential Hh target genes that were identified in the mouse. These are lama1, encoding Laminin α1, and c125, a novel gene hypothesised to play a role in motor neuron development. Laminins are conserved heterotrimeric glycoproteins, of which there are at least 16 different isoforms, generated from Laminin α, β, and γ subunits. Laminins are an essential component of basement membranes (BMs), which are specialised forms of the extra-cellular matrix (ECM) crucial for normal patterning, proliferation, migration, and differentiation of many different cell types. Mutations in lama1 cause embryonic lethality in mouse and zebrafish, demonstrating that Laminin α1 function is critical for embryonic development. The aims of this study were to assess the expression of lama1 and c125 during zebrafish embryonic development, and to explore a possible role for Shh in their regulation. I also aimed to determine the regulatory sequences controlling lama1 expression using a bacterial artificial chromosome (BAC) transgenic zebrafish approach. My data reveal that the enhancer elements controlling zebrafish lama1 expression are located within intron 1 of lama1. Within this intron, I have uncoupled the enhancers that regulate lama1 expression in the muscle fibres, from enhancers that regulate lama1 expression in the anterior CNS, neural tube, and the eye. These findings are of particular importance because ectopic expression of lama1 in mouse models of congenital muscular dystrophy restores normal muscle function. Therefore, the characterisation of lama1 regulation provides a framework for future studies to identify drugs stimulating endogenous lama1 expression in dystrophic muscles.
Metadata
Publicly visible additional information: | joe.b.pick@gmail.com |
---|---|
Awarding institution: | University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Biomedical Science (Sheffield) |
Identification Number/EthosID (e.g. uk.bl.ethos.123456): | uk.bl.ethos.570106 |
Depositing User: | Mr Joseph Pickering |
Date Deposited: | 22 Apr 2013 14:30 |
Last Modified: | 12 Oct 2018 09:18 |
Downloads
Contents
Filename: Contents.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Chapter_1
Filename: Chapter_1.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Chapter_2
Filename: Chapter_2.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Chapter_2.2
Filename: Chapter_2.2.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Chapter_2.3pdf
Filename: Chapter_2.3pdf.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch3_intro
Filename: Ch3_intro.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
ch3_results
Filename: ch3_results.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch3_discussion
Filename: Ch3_discussion.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch4_intro
Filename: Ch4_intro.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch4_results
Filename: Ch4_results.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch4_discussion
Filename: Ch4_discussion.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch5_introduction
Filename: Ch5_introduction.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch5_results
Filename: Ch5_results.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch5_discussion
Filename: Ch5_discussion.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Chapter_6_intro
Filename: Chapter_6_intro.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Chapter_6_Results.pdf
Filename: Chapter_6_Results.pdf.zip
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch6_discussion
Filename: Ch6_discussion.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
Ch7_final_discussion
Filename: Ch7_final_discussion.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
bibliography
Filename: bibliography.pdf
Licence: Creative Commons Attribution Non-commercial No Derivatives (UK)
You do not need to contact us to get a copy of this thesis. Please use the 'Download' link(s) above to get a copy.
You can contact us about this thesis. If you need to make a general enquiry, please see the Contact us page.