A mathematical model of the role of aggregation in sonic hedgehog signalling

Derrick, D. J. A., Wolton, K., Currie, R. A. and Tindall, M. J. (2021) A mathematical model of the role of aggregation in sonic hedgehog signalling. PLoS computational biology, 17 (2). e1008562. ISSN 1553-7358 doi: 10.1371/journal.pcbi.1008562

Abstract/Summary

Effective regulation of the sonic hedgehog (Shh) signalling pathway is essential for normal development in a wide variety of species. Correct Shh signalling requires the formation of Shh aggregates on the surface of producing cells. Shh aggregates subsequently diffuse away and are recognised in receiving cells located elsewhere in the developing embryo. Various mechanisms have been postulated regarding how these aggregates form and what their precise role is in the overall signalling process. To understand the role of these mechanisms in the overall signalling process, we formulate and analyse a mathematical model of Shh aggregation using nonlinear ordinary differential equations. We consider Shh aggregate formation to comprise of multimerisation, association with heparan sulfate proteoglycans (HSPG) and binding with lipoproteins. We show that the size distribution of the Shh aggregates formed on the producing cell surface resembles an exponential distribution, a result in agreement with experimental data. A detailed sensitivity analysis of our model reveals that this exponential distribution is robust to parameter changes, and subsequently, also to variations in the processes by which Shh is recruited by HSPGs and lipoproteins. The work demonstrates the time taken for different sized Shh aggregates to form and the important role this likely plays in Shh diffusion.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/96928
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Science > School of Mathematical, Physical and Computational Sciences > Department of Mathematics and Statistics
Publisher	Plos
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