Stable developmental patterns of gene expression without morphogen gradients.
Gene expression patterns in developing organisms are established by groups of cross-regulating target genes that are driven by morphogen gradients. As development progresses, morphogen activity is reduced, leaving the emergent pattern without stabilizing positional cues and at risk of rapid deterior...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-12-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1012555 |
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| author | Maciej Majka Nils B Becker Pieter Rein Ten Wolde Marcin Zagorski Thomas R Sokolowski |
| author_facet | Maciej Majka Nils B Becker Pieter Rein Ten Wolde Marcin Zagorski Thomas R Sokolowski |
| author_sort | Maciej Majka |
| collection | DOAJ |
| description | Gene expression patterns in developing organisms are established by groups of cross-regulating target genes that are driven by morphogen gradients. As development progresses, morphogen activity is reduced, leaving the emergent pattern without stabilizing positional cues and at risk of rapid deterioration due to the inherently noisy biochemical processes at the cellular level. But remarkably, gene expression patterns remain spatially stable and reproducible over long developmental time spans in many biological systems. Here we combine spatial-stochastic simulations with an enhanced sampling method (Non-Stationary Forward Flux Sampling) and a recently developed stability theory to address how spatiotemporal integrity of a gene expression pattern is maintained in developing tissue lacking morphogen gradients. Using a minimal embryo model consisting of spatially coupled biochemical reactor volumes, we study a prototypical stripe pattern in which weak cross-repression between nearest neighbor expression domains alternates with strong repression between next-nearest neighbor domains, inspired by the gap gene system in the Drosophila embryo. We find that tuning of the weak repressive interactions to an optimal level can prolong stability of the expression patterns by orders of magnitude, enabling stable patterns over developmentally relevant times in the absence of morphogen gradients. The optimal parameter regime found in simulations of the embryo model closely agrees with the predictions of our coarse-grained stability theory. To elucidate the origin of stability, we analyze a reduced phase space defined by two measures of pattern asymmetry. We find that in the optimal regime, intact patterns are protected via restoring forces that counteract random perturbations and give rise to a metastable basin. Together, our results demonstrate that metastable attractors can emerge as a property of stochastic gene expression patterns even without system-wide positional cues, provided that the gene regulatory interactions shaping the pattern are optimally tuned. |
| format | Article |
| id | doaj-art-2f97057dd78547f2a14fd3556d33cba7 |
| institution | DOAJ |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-2f97057dd78547f2a14fd3556d33cba72025-08-20T02:45:06ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582024-12-012012e101255510.1371/journal.pcbi.1012555Stable developmental patterns of gene expression without morphogen gradients.Maciej MajkaNils B BeckerPieter Rein Ten WoldeMarcin ZagorskiThomas R SokolowskiGene expression patterns in developing organisms are established by groups of cross-regulating target genes that are driven by morphogen gradients. As development progresses, morphogen activity is reduced, leaving the emergent pattern without stabilizing positional cues and at risk of rapid deterioration due to the inherently noisy biochemical processes at the cellular level. But remarkably, gene expression patterns remain spatially stable and reproducible over long developmental time spans in many biological systems. Here we combine spatial-stochastic simulations with an enhanced sampling method (Non-Stationary Forward Flux Sampling) and a recently developed stability theory to address how spatiotemporal integrity of a gene expression pattern is maintained in developing tissue lacking morphogen gradients. Using a minimal embryo model consisting of spatially coupled biochemical reactor volumes, we study a prototypical stripe pattern in which weak cross-repression between nearest neighbor expression domains alternates with strong repression between next-nearest neighbor domains, inspired by the gap gene system in the Drosophila embryo. We find that tuning of the weak repressive interactions to an optimal level can prolong stability of the expression patterns by orders of magnitude, enabling stable patterns over developmentally relevant times in the absence of morphogen gradients. The optimal parameter regime found in simulations of the embryo model closely agrees with the predictions of our coarse-grained stability theory. To elucidate the origin of stability, we analyze a reduced phase space defined by two measures of pattern asymmetry. We find that in the optimal regime, intact patterns are protected via restoring forces that counteract random perturbations and give rise to a metastable basin. Together, our results demonstrate that metastable attractors can emerge as a property of stochastic gene expression patterns even without system-wide positional cues, provided that the gene regulatory interactions shaping the pattern are optimally tuned.https://doi.org/10.1371/journal.pcbi.1012555 |
| spellingShingle | Maciej Majka Nils B Becker Pieter Rein Ten Wolde Marcin Zagorski Thomas R Sokolowski Stable developmental patterns of gene expression without morphogen gradients. PLoS Computational Biology |
| title | Stable developmental patterns of gene expression without morphogen gradients. |
| title_full | Stable developmental patterns of gene expression without morphogen gradients. |
| title_fullStr | Stable developmental patterns of gene expression without morphogen gradients. |
| title_full_unstemmed | Stable developmental patterns of gene expression without morphogen gradients. |
| title_short | Stable developmental patterns of gene expression without morphogen gradients. |
| title_sort | stable developmental patterns of gene expression without morphogen gradients |
| url | https://doi.org/10.1371/journal.pcbi.1012555 |
| work_keys_str_mv | AT maciejmajka stabledevelopmentalpatternsofgeneexpressionwithoutmorphogengradients AT nilsbbecker stabledevelopmentalpatternsofgeneexpressionwithoutmorphogengradients AT pieterreintenwolde stabledevelopmentalpatternsofgeneexpressionwithoutmorphogengradients AT marcinzagorski stabledevelopmentalpatternsofgeneexpressionwithoutmorphogengradients AT thomasrsokolowski stabledevelopmentalpatternsofgeneexpressionwithoutmorphogengradients |