Cargando…

The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network

Understanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ called Pax6, which is both necessary and sufficient for eye development. Yet precisely how P...

Descripción completa

Detalles Bibliográficos
Autores principales: Grocott, Timothy, Lozano-Velasco, Estefania, Mok, Gi Fay, Münsterberg, Andrea E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774904/
https://www.ncbi.nlm.nih.gov/pubmed/33214222
http://dx.doi.org/10.1242/dev.185827
_version_ 1783630358138322944
author Grocott, Timothy
Lozano-Velasco, Estefania
Mok, Gi Fay
Münsterberg, Andrea E.
author_facet Grocott, Timothy
Lozano-Velasco, Estefania
Mok, Gi Fay
Münsterberg, Andrea E.
author_sort Grocott, Timothy
collection PubMed
description Understanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ called Pax6, which is both necessary and sufficient for eye development. Yet precisely how Pax6 achieves this deeply homologous function is poorly understood. Using the chick as a model organism, we show that vertebrate Pax6 interacts with a pair of morphogen-coding genes, Tgfb2 and Fst, to form a putative Turing network, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the first organisational axis of the eye and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independently of the highly ordered tissue interactions that help to assemble the eye in vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cups in vitro. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies.
format Online
Article
Text
id pubmed-7774904
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Company of Biologists Ltd
record_format MEDLINE/PubMed
spelling pubmed-77749042021-01-05 The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network Grocott, Timothy Lozano-Velasco, Estefania Mok, Gi Fay Münsterberg, Andrea E. Development Research Article Understanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ called Pax6, which is both necessary and sufficient for eye development. Yet precisely how Pax6 achieves this deeply homologous function is poorly understood. Using the chick as a model organism, we show that vertebrate Pax6 interacts with a pair of morphogen-coding genes, Tgfb2 and Fst, to form a putative Turing network, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the first organisational axis of the eye and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independently of the highly ordered tissue interactions that help to assemble the eye in vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cups in vitro. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies. The Company of Biologists Ltd 2020-12-23 /pmc/articles/PMC7774904/ /pubmed/33214222 http://dx.doi.org/10.1242/dev.185827 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This 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.
spellingShingle Research Article
Grocott, Timothy
Lozano-Velasco, Estefania
Mok, Gi Fay
Münsterberg, Andrea E.
The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network
title The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network
title_full The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network
title_fullStr The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network
title_full_unstemmed The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network
title_short The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network
title_sort pax6 master control gene initiates spontaneous retinal development via a self-organising turing network
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774904/
https://www.ncbi.nlm.nih.gov/pubmed/33214222
http://dx.doi.org/10.1242/dev.185827
work_keys_str_mv AT grocotttimothy thepax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT lozanovelascoestefania thepax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT mokgifay thepax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT munsterbergandreae thepax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT grocotttimothy pax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT lozanovelascoestefania pax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT mokgifay pax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork
AT munsterbergandreae pax6mastercontrolgeneinitiatesspontaneousretinaldevelopmentviaaselforganisingturingnetwork