<i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate
<i>Nkx2.9</i> is a member of the NK homeobox family and resembles <i>Nkx2.2</i> both in homology and expression pattern. However, while <i>Nkx2.2</i> is required for development of serotonergic neurons, the role of <i>Nkx2.9</i> in the mid-hindbrain re...
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| Format: | Article |
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2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12663 |
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| author | Willemieke M. Kouwenhoven Lars von Oerthel Maria Gruppilo Jianmin Tian Cindy M. R. J. Wagemans Imke G. J. Houwers Joseph Locker Simone Mesman Marten P. Smidt |
| author_facet | Willemieke M. Kouwenhoven Lars von Oerthel Maria Gruppilo Jianmin Tian Cindy M. R. J. Wagemans Imke G. J. Houwers Joseph Locker Simone Mesman Marten P. Smidt |
| author_sort | Willemieke M. Kouwenhoven |
| collection | DOAJ |
| description | <i>Nkx2.9</i> is a member of the NK homeobox family and resembles <i>Nkx2.2</i> both in homology and expression pattern. However, while <i>Nkx2.2</i> is required for development of serotonergic neurons, the role of <i>Nkx2.9</i> in the mid-hindbrain region is still ill-defined. We have previously shown that <i>Nkx2.9</i> expression is downregulated upon loss of <i>En1</i> during development. Here, we determined whether mdDA neurons require <i>Nkx2.9</i> during their development. We show that <i>Nkx2.9</i> is strongly expressed in the IsO and in the VZ and SVZ of the embryonic midbrain, and the majority of mdDA neurons expressed <i>Nkx2.9</i> during their development. Although the expression of <i>Dat</i> and <i>Cck</i> are slightly affected during development, the overall development and cytoarchitecture of TH-expressing neurons is not affected in the adult <i>Nkx2.9</i>-depleted midbrain. Transcriptome analysis at E14.5 indicated that genes involved in mid- and hindbrain development are affected by <i>Nkx2.9</i>-ablation, such as <i>Wnt8b</i> and <i>Tph2</i>. Although the expression of <i>Tph2</i> extends more rostral into the isthmic area in the <i>Nkx2.9</i> mutants, the establishment of the IsO is not affected. Taken together, these data point to a minor role for <i>Nkx2.9</i> in mid-hindbrain patterning by repressing a hindbrain-specific cell-fate in the IsO and by subtle regulation of mdDA neuronal subset specification. |
| first_indexed | 2024-03-10T04:53:02Z |
| format | Article |
| id | doaj.art-283aba92b0534e03b7fabca0de5e27a2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:02Z |
| publishDate | 2021-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-283aba92b0534e03b7fabca0de5e27a22023-11-23T02:26:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231266310.3390/ijms222312663<i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-FateWillemieke M. Kouwenhoven0Lars von Oerthel1Maria Gruppilo2Jianmin Tian3Cindy M. R. J. Wagemans4Imke G. J. Houwers5Joseph Locker6Simone Mesman7Marten P. Smidt8Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsSwammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Pathology, University of Pittsburgh, Pittsburgh, PA 15260, USASwammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsSwammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA 15260, USASwammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsSwammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands<i>Nkx2.9</i> is a member of the NK homeobox family and resembles <i>Nkx2.2</i> both in homology and expression pattern. However, while <i>Nkx2.2</i> is required for development of serotonergic neurons, the role of <i>Nkx2.9</i> in the mid-hindbrain region is still ill-defined. We have previously shown that <i>Nkx2.9</i> expression is downregulated upon loss of <i>En1</i> during development. Here, we determined whether mdDA neurons require <i>Nkx2.9</i> during their development. We show that <i>Nkx2.9</i> is strongly expressed in the IsO and in the VZ and SVZ of the embryonic midbrain, and the majority of mdDA neurons expressed <i>Nkx2.9</i> during their development. Although the expression of <i>Dat</i> and <i>Cck</i> are slightly affected during development, the overall development and cytoarchitecture of TH-expressing neurons is not affected in the adult <i>Nkx2.9</i>-depleted midbrain. Transcriptome analysis at E14.5 indicated that genes involved in mid- and hindbrain development are affected by <i>Nkx2.9</i>-ablation, such as <i>Wnt8b</i> and <i>Tph2</i>. Although the expression of <i>Tph2</i> extends more rostral into the isthmic area in the <i>Nkx2.9</i> mutants, the establishment of the IsO is not affected. Taken together, these data point to a minor role for <i>Nkx2.9</i> in mid-hindbrain patterning by repressing a hindbrain-specific cell-fate in the IsO and by subtle regulation of mdDA neuronal subset specification.https://www.mdpi.com/1422-0067/22/23/12663<i>Nkx2.9</i><i>Nkx2.8</i>mdDAIsOmouse<i>Wnt8b</i> |
| spellingShingle | Willemieke M. Kouwenhoven Lars von Oerthel Maria Gruppilo Jianmin Tian Cindy M. R. J. Wagemans Imke G. J. Houwers Joseph Locker Simone Mesman Marten P. Smidt <i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate International Journal of Molecular Sciences <i>Nkx2.9</i> <i>Nkx2.8</i> mdDA IsO mouse <i>Wnt8b</i> |
| title | <i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate |
| title_full | <i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate |
| title_fullStr | <i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate |
| title_full_unstemmed | <i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate |
| title_short | <i>Nkx2.9</i> Contributes to Mid-Hindbrain Patterning by Regulation of mdDA Neuronal Cell-Fate and Repression of a Hindbrain-Specific Cell-Fate |
| title_sort | i nkx2 9 i contributes to mid hindbrain patterning by regulation of mdda neuronal cell fate and repression of a hindbrain specific cell fate |
| topic | <i>Nkx2.9</i> <i>Nkx2.8</i> mdDA IsO mouse <i>Wnt8b</i> |
| url | https://www.mdpi.com/1422-0067/22/23/12663 |
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