How the skeleton makes its shape: combining genetic and mathematical models

Karen Liu (primary)
Centre for Craniofacial and Regenerative Biology
King's College London
Karen Page (secondary)
Mathematics
UCL

Abstract

The head is made up of multiple skeletal elements and birth defects affecting these bones and cartilages can be catastrophic. We have very little understanding of what controls the size and shape of these irregular skeletal forms. A better understanding of this control will improve our treatment of craniofacial anomalies and future efforts in repair and regeneration of skeletal forms. In this project, we combine genetically modified mouse models (Liu) with nano-patterning approaches (Chiappini) to study shape changes in condensing mesenchyme. These allow us to mathematically model (Page) formation of the skeletal elements. Overall the goal is to understand characteristic facial changes in human ciliopathy patients.


References

References:
1. Onesto, V. Barrell, WB, Okesola, M, Amato F, Gentile F, Liu KJ, Chiappini. Biomedical Microdevices 21, 2019. A quantitative approach for determining the role of geometrical constraints when shaping mesenchymal condensations.
2. Tabler et al., Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF-related syndromes. Developmental Cell 2013
3. Adel Al-Lami, Barrell and Liu, Micrognathia in mouse models of ciliopathies Bioch Soc Trans 2016
4. Glimm, Headon and Kiskowski, Computational and Mathematical Models of Chondrogenesis in Vertebrate Limbs Birth Defects Research 2012
5. Christley et al., Patterns of mesenchymal condensation in a multiscale, discrete stochastic model Plos Computational Biology 2007
6. Raspopvic et al., Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients Science 2014


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
BiotechnologyDevelopment
Techniques & Approaches
EngineeringGeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling