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Mathematical Modelling of Digit Patterning in Mouse Limb Development.
KTH, School of Computer Science and Communication (CSC).
2012 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The morphology of limbs can provide valuable evolutionary insights in vertebrate development. Despite the wide variety of shapes and sizes across the tree of life, the underlying biological mechanism of digit formation is conserved. Due to its easy access on an embryo, developmental biologists have been able to do experiments in chicken, mice limbs that identified key regulatory networks and common principles of development. The complexity of these networks makes it difficult to understand and predict the emergence of phenotypes by verbal reasoning alone. The scope of this study is to build a computational model that is based on known interactions and is able to summarize its output in agreement with available experimental data. The set of available regulatory interactions is formulated using partial differential equations of reaction diffusion type solved on a realistic domain extracted from limb bud images of mouse embryos. The emerging pattern is of turing type. To strengthen the validity of the model, wild-type and mutant phenotypes of the limb are successfully simulated and reproduced.

Abstract [sv]

Genom morfologiska studier kan vi få värdeful insikt i evolutionen av den embryoniska utvecklingen hos ryggradsdjur. Trots att storlek och form skiljer sig mellan olika arter av ryggradsdjur så är de underliggande biologiska mekanismerna för organutveckling gemensamma. Utvecklingsbiologer har genom experiment på kyckling- och musembryon identifierat grundläggande principer för organutveckling samt viktiga regulatoriska nätverk. Dessvärre är komplexiteten av dessa nätverk såpass hög att det är svårt att förutsäga utfall enbart baserat på verbala resonemang. Målet med denna studie var att konstruera en kvantitativ modell, baserad på kända regulatoriska interaktioner, som kan reproducera experimentella data. Vi transformerade en uppsättning regulatoriska interaktioner till en uppsättning av partiella differentialekvationer av diffusionsreaktionstyp, och löste dem sedan i en realistisk domän baserad på bilder av extremitetsutskott i musembryon. Vi visade att utvecklingsmönstret var av Turingtyp. För att ytterligare validera vår modell så simulerade vi med positivt resultat observerade fenotyper i wild-type såväl som i benutvecklingsmutanter.

Place, publisher, year, edition, pages
2012.
Series
Trita-CSC-E, ISSN 1653-5715 ; 2012:007
National Category
Computer Science
Identifiers
URN: urn:nbn:se:kth:diva-130914OAI: oai:DiVA.org:kth-130914DiVA: diva2:654360
Educational program
Master of Science - Computational and Systems Biology
Uppsok
Technology
Supervisors
Examiners
Available from: 2013-10-07 Created: 2013-10-07

Open Access in DiVA

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Other links

http://www.nada.kth.se/utbildning/grukth/exjobb/rapportlistor/2012/rapporter12/badugu_amarendra_12007.pdf
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