Modeling binary and graded cone cell fate patterning in the mouse retina.
Nervous systems are incredibly diverse, with myriad neuronal subtypes defined by gene expression. How binary and graded fate characteristics are patterned across tissues is poorly understood. Expression of opsin photopigments in the cone photoreceptors of the mouse retina provides an excellent model...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1007691 |
| _version_ | 1818581862443909120 |
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| author | Kiara C Eldred Cameron Avelis Robert J Johnston Elijah Roberts |
| author_facet | Kiara C Eldred Cameron Avelis Robert J Johnston Elijah Roberts |
| author_sort | Kiara C Eldred |
| collection | DOAJ |
| description | Nervous systems are incredibly diverse, with myriad neuronal subtypes defined by gene expression. How binary and graded fate characteristics are patterned across tissues is poorly understood. Expression of opsin photopigments in the cone photoreceptors of the mouse retina provides an excellent model to address this question. Individual cones express S-opsin only, M-opsin only, or both S-opsin and M-opsin. These cell populations are patterned along the dorsal-ventral axis, with greater M-opsin expression in the dorsal region and greater S-opsin expression in the ventral region. Thyroid hormone signaling plays a critical role in activating M-opsin and repressing S-opsin. Here, we developed an image analysis approach to identify individual cone cells and evaluate their opsin expression from immunofluorescence imaging tiles spanning roughly 6 mm along the D-V axis of the mouse retina. From analyzing the opsin expression of ~250,000 cells, we found that cones make a binary decision between S-opsin only and co-expression competent fates. Co-expression competent cells express graded levels of S- and M-opsins, depending nonlinearly on their position in the dorsal-ventral axis. M- and S-opsin expression display differential, inverse patterns. Using these single-cell data, we developed a quantitative, probabilistic model of cone cell decisions in the retinal tissue based on thyroid hormone signaling activity. The model recovers the probability distribution for cone fate patterning in the mouse retina and describes a minimal set of interactions that are necessary to reproduce the observed cell fates. Our study provides a paradigm describing how differential responses to regulatory inputs generate complex patterns of binary and graded cell fates. |
| first_indexed | 2024-12-16T07:40:14Z |
| format | Article |
| id | doaj.art-fac39a1186d043e78a0fc1d01a28b41d |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-16T07:40:14Z |
| publishDate | 2020-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-fac39a1186d043e78a0fc1d01a28b41d2022-12-21T22:39:06ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582020-03-01163e100769110.1371/journal.pcbi.1007691Modeling binary and graded cone cell fate patterning in the mouse retina.Kiara C EldredCameron AvelisRobert J JohnstonElijah RobertsNervous systems are incredibly diverse, with myriad neuronal subtypes defined by gene expression. How binary and graded fate characteristics are patterned across tissues is poorly understood. Expression of opsin photopigments in the cone photoreceptors of the mouse retina provides an excellent model to address this question. Individual cones express S-opsin only, M-opsin only, or both S-opsin and M-opsin. These cell populations are patterned along the dorsal-ventral axis, with greater M-opsin expression in the dorsal region and greater S-opsin expression in the ventral region. Thyroid hormone signaling plays a critical role in activating M-opsin and repressing S-opsin. Here, we developed an image analysis approach to identify individual cone cells and evaluate their opsin expression from immunofluorescence imaging tiles spanning roughly 6 mm along the D-V axis of the mouse retina. From analyzing the opsin expression of ~250,000 cells, we found that cones make a binary decision between S-opsin only and co-expression competent fates. Co-expression competent cells express graded levels of S- and M-opsins, depending nonlinearly on their position in the dorsal-ventral axis. M- and S-opsin expression display differential, inverse patterns. Using these single-cell data, we developed a quantitative, probabilistic model of cone cell decisions in the retinal tissue based on thyroid hormone signaling activity. The model recovers the probability distribution for cone fate patterning in the mouse retina and describes a minimal set of interactions that are necessary to reproduce the observed cell fates. Our study provides a paradigm describing how differential responses to regulatory inputs generate complex patterns of binary and graded cell fates.https://doi.org/10.1371/journal.pcbi.1007691 |
| spellingShingle | Kiara C Eldred Cameron Avelis Robert J Johnston Elijah Roberts Modeling binary and graded cone cell fate patterning in the mouse retina. PLoS Computational Biology |
| title | Modeling binary and graded cone cell fate patterning in the mouse retina. |
| title_full | Modeling binary and graded cone cell fate patterning in the mouse retina. |
| title_fullStr | Modeling binary and graded cone cell fate patterning in the mouse retina. |
| title_full_unstemmed | Modeling binary and graded cone cell fate patterning in the mouse retina. |
| title_short | Modeling binary and graded cone cell fate patterning in the mouse retina. |
| title_sort | modeling binary and graded cone cell fate patterning in the mouse retina |
| url | https://doi.org/10.1371/journal.pcbi.1007691 |
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