<i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons
During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of <i>Tcf4</i>, a member of the E-box protein...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/3/317 |
| _version_ | 1797540593645125632 |
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| author | Simone Mesman Iris Wever Marten P. Smidt |
| author_facet | Simone Mesman Iris Wever Marten P. Smidt |
| author_sort | Simone Mesman |
| collection | DOAJ |
| description | During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of <i>Tcf4</i>, a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that <i>Tcf4</i> is expressed throughout development, but is no longer detected in adult midbrain. Deletion of <i>Tcf4</i> results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker <i>Nxph3</i> and rostral subset marker <i>Ahd2</i> are affected at E14.5, indicating that <i>Tcf4</i> is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of <i>Th</i> transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor <i>Ascl1</i>, known for its role in mdDA neuronal differentiation, upon loss of <i>Tcf4</i>. Taken together, our data identified a minor role for <i>Tcf4</i> in mdDA neuronal development and subset specification. |
| first_indexed | 2024-03-10T13:03:24Z |
| format | Article |
| id | doaj.art-f0cef2b68da34b89904cff89c68b0f0e |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T13:03:24Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-f0cef2b68da34b89904cff89c68b0f0e2023-11-21T11:20:40ZengMDPI AGBiomedicines2227-90592021-03-019331710.3390/biomedicines9030317<i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic NeuronsSimone Mesman0Iris Wever1Marten P. Smidt2Swammerdam Institute for Life Sciences, FNWI, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsSwammerdam Institute for Life Sciences, FNWI, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsSwammerdam Institute for Life Sciences, FNWI, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsDuring development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of <i>Tcf4</i>, a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that <i>Tcf4</i> is expressed throughout development, but is no longer detected in adult midbrain. Deletion of <i>Tcf4</i> results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker <i>Nxph3</i> and rostral subset marker <i>Ahd2</i> are affected at E14.5, indicating that <i>Tcf4</i> is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of <i>Th</i> transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor <i>Ascl1</i>, known for its role in mdDA neuronal differentiation, upon loss of <i>Tcf4</i>. Taken together, our data identified a minor role for <i>Tcf4</i> in mdDA neuronal development and subset specification.https://www.mdpi.com/2227-9059/9/3/317midbrain developmentdopamine neurons<i>Tcf4</i>subset specificationbHLH factors |
| spellingShingle | Simone Mesman Iris Wever Marten P. Smidt <i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons Biomedicines midbrain development dopamine neurons <i>Tcf4</i> subset specification bHLH factors |
| title | <i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons |
| title_full | <i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons |
| title_fullStr | <i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons |
| title_full_unstemmed | <i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons |
| title_short | <i>Tcf4</i> Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons |
| title_sort | i tcf4 i is involved in subset specification of mesodiencephalic dopaminergic neurons |
| topic | midbrain development dopamine neurons <i>Tcf4</i> subset specification bHLH factors |
| url | https://www.mdpi.com/2227-9059/9/3/317 |
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