The University of Dublin | Trinity College -- Ollscoil Átha Cliath | Coláiste na Tríonóide
Trinity's Access to Research Archive
Home :: Log In :: Submit :: Alerts ::

TARA >
School of Natural Science >
Zoology >
Zoology (Scholarly Publications) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/39557

Title: Identification of Mechanosensitive Genes during Embryonic Bone Formation.
Author: PRENDERGAST, PATRICK JOHN
MURPHY, PAULA
Sponsor: Irish Research Council for Science Engineering and Technology
Author's Homepage: http://people.tcd.ie/pmurphy3
http://people.tcd.ie/pprender
Keywords: Biochemical Research Methods
Mathematical & Computational Biology
Issue Date: 2008
Citation: Nowlan, N., Prendergast P.J. and Murphy, P., Identification of Mechanosensitive Genes during Embryonic Bone Formation., PLoS Computational Biology, 4, 12, 2008, e1000250-
Series/Report no.: PLoS Computational Biology
4
12
Abstract: Although it is known that mechanical forces are needed for normal bone development, the current understanding of how biophysical stimuli are interpreted by and integrated with genetic regulatory mechanisms is limited. Mechanical forces are thought to be mediated in cells by "mechanosensitive" genes, but it is a challenge to demonstrate that the genetic regulation of the biological system is dependant on particular mechanical forces in vivo. We propose a new means of selecting candidate mechanosensitive genes by comparing in vivo gene expression patterns with patterns of biophysical stimuli, computed using finite element analysis. In this study, finite element analyses of the avian embryonic limb were performed using anatomically realistic rudiment and muscle morphologies, and patterns of biophysical stimuli were compared with the expression patterns of four candidate mechanosensitive genes integral to bone development. The expression patterns of two genes, Collagen X (ColX) and Indian hedgehog (Ihh), were shown to colocalise with biophysical stimuli induced by embryonic muscle contractions, identifying them as potentially being involved in the mechanoregulation of bone formation. An altered mechanical environment was induced in the embryonic chick, where a neuromuscular blocking agent was administered in ovo to modify skeletal muscle contractions. Finite element analyses predicted dramatic changes in levels and patterns of biophysical stimuli, and a number of immobilised specimens exhibited differences in ColX and Ihh expression. The results obtained indicate that computationally derived patterns of biophysical stimuli can be used to inform a directed search for genes that may play a mechanoregulatory role in particular in vivo events or processes. Furthermore, the experimental data demonstrate that ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators in translating information from the mechanical environment to the molecular regulation of bone formation in the embryo.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/39557
Related links: http://dx.doi.org/10.1371/journal.pcbi.1000250
Appears in Collections:Zoology (Scholarly Publications)

Files in This Item:

File Description SizeFormat
Identification of Mechanosensitive Genes during Embryonic Bone Formation.pdfPublished (publisher's copy) - Peer Reviewed883.34 kBAdobe PDFView/Open


This item is protected by original copyright


Please note: There is a known bug in some browsers that causes an error when a user tries to view large pdf file within the browser window. If you receive the message "The file is damaged and could not be repaired", please try one of the solutions linked below based on the browser you are using.

Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback