Economou, A.D., Monk, N.A.M. orcid.org/0000-0002-5465-4857 and Green, J.B.A. (2020) Perturbation analysis of a multi-morphogen Turing reaction-diffusion stripe patterning system reveals key regulatory interactions. Development, 147 (20). dev190553. ISSN 0950-1991
Abstract
Periodic patterning is widespread in development and can be modelled by reaction-diffusion (RD) processes. However, minimal two-component RD descriptions are vastly simpler than the multi-molecular events that actually occur and are often hard to relate to real interactions measured experimentally. Addressing these issues, we investigated the periodic striped patterning of the rugae (transverse ridges) in the mammalian oral palate, focusing on multiple previously implicated pathways: FGF, Hh, Wnt and BMP. For each, we experimentally identified spatial patterns of activity and distinct responses of the system to inhibition. Through numerical and analytical approaches, we were able to constrain substantially the number of network structures consistent with the data. Determination of the dynamics of pattern appearance further revealed its initiation by ‘activators’ FGF and Wnt, and ‘inhibitor’ Hh, whereas BMP and mesenchyme-specific-FGF signalling were incorporated once stripes were formed. This further limited the number of possible networks. Experimental constraint thus limited the number of possible minimal networks to 154, just 0.004% of the number of possible diffusion-driven instability networks. Together, these studies articulate the principles of multi-morphogen RD patterning and demonstrate the utility of perturbation analysis for constraining RD systems.
This article has an associated ‘The people behind the papers’ interview.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2020. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Morphogens; Palate; Patterning; Reaction-diffusion; Rugae |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Nov 2020 15:39 |
Last Modified: | 13 Nov 2020 15:39 |
Status: | Published |
Publisher: | The Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/dev.190553 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167977 |