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Quantitative assessment of computational models for retinotopic map formation

Molecular and activity‐based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not we...

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Autores principales: Hjorth, J J Johannes, Sterratt, David C, Cutts, Catherine S, Willshaw, David J, Eglen, Stephen J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497816/
https://www.ncbi.nlm.nih.gov/pubmed/25367067
http://dx.doi.org/10.1002/dneu.22241
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author Hjorth, J J Johannes
Sterratt, David C
Cutts, Catherine S
Willshaw, David J
Eglen, Stephen J
author_facet Hjorth, J J Johannes
Sterratt, David C
Cutts, Catherine S
Willshaw, David J
Eglen, Stephen J
author_sort Hjorth, J J Johannes
collection PubMed
description Molecular and activity‐based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not well understood. We have developed a framework within which existing computational models can be assessed in an unbiased and quantitative manner against a set of experimental data curated from the mouse retinocollicular system. Our framework facilitates comparison between models, testing new models against known phenotypes and simulating new phenotypes in existing models. We have used this framework to assess four representative models that combine Eph/ephrin gradients and/or activity‐based mechanisms and competition. Two of the models were updated from their original form to fit into our framework. The models were tested against five different phenotypes: wild type, Isl2‐EphA3 (ki/ki), Isl2‐EphA3 (ki/+), ephrin‐A2,A3,A5 triple knock‐out (TKO), and Math5 (−/−) (Atoh7). Two models successfully reproduced the extent of the Math5 (−/−) anteromedial projection, but only one of those could account for the collapse point in Isl2‐EphA3 (ki/+). The models needed a weak anteroposterior gradient in the SC to reproduce the residual order in the ephrin‐A2,A3,A5 TKO phenotype, suggesting either an incomplete knock‐out or the presence of another guidance molecule. Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 641–666, 2015
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spelling pubmed-44978162015-07-09 Quantitative assessment of computational models for retinotopic map formation Hjorth, J J Johannes Sterratt, David C Cutts, Catherine S Willshaw, David J Eglen, Stephen J Dev Neurobiol Research Articles Molecular and activity‐based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not well understood. We have developed a framework within which existing computational models can be assessed in an unbiased and quantitative manner against a set of experimental data curated from the mouse retinocollicular system. Our framework facilitates comparison between models, testing new models against known phenotypes and simulating new phenotypes in existing models. We have used this framework to assess four representative models that combine Eph/ephrin gradients and/or activity‐based mechanisms and competition. Two of the models were updated from their original form to fit into our framework. The models were tested against five different phenotypes: wild type, Isl2‐EphA3 (ki/ki), Isl2‐EphA3 (ki/+), ephrin‐A2,A3,A5 triple knock‐out (TKO), and Math5 (−/−) (Atoh7). Two models successfully reproduced the extent of the Math5 (−/−) anteromedial projection, but only one of those could account for the collapse point in Isl2‐EphA3 (ki/+). The models needed a weak anteroposterior gradient in the SC to reproduce the residual order in the ephrin‐A2,A3,A5 TKO phenotype, suggesting either an incomplete knock‐out or the presence of another guidance molecule. Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 641–666, 2015 John Wiley and Sons Inc. 2014-11-14 2015-06 /pmc/articles/PMC4497816/ /pubmed/25367067 http://dx.doi.org/10.1002/dneu.22241 Text en © 2014 Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/3.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hjorth, J J Johannes
Sterratt, David C
Cutts, Catherine S
Willshaw, David J
Eglen, Stephen J
Quantitative assessment of computational models for retinotopic map formation
title Quantitative assessment of computational models for retinotopic map formation
title_full Quantitative assessment of computational models for retinotopic map formation
title_fullStr Quantitative assessment of computational models for retinotopic map formation
title_full_unstemmed Quantitative assessment of computational models for retinotopic map formation
title_short Quantitative assessment of computational models for retinotopic map formation
title_sort quantitative assessment of computational models for retinotopic map formation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497816/
https://www.ncbi.nlm.nih.gov/pubmed/25367067
http://dx.doi.org/10.1002/dneu.22241
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