Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish
In the spinal cord, excitatory V2a and inhibitory V2b interneurons are produced together by the final division of common P2 progenitors. During V2a and V2b diversification, Tal1 is necessary and sufficient to promote V2b differentiation and Vsx2 suppresses the expression of motor neuron genes to con...
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/10/3600 |
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| author | Qi Zhang Haomang Xu Wei Zhao Jianbo Zheng Lei Sun Chen Luo |
| author_facet | Qi Zhang Haomang Xu Wei Zhao Jianbo Zheng Lei Sun Chen Luo |
| author_sort | Qi Zhang |
| collection | DOAJ |
| description | In the spinal cord, excitatory V2a and inhibitory V2b interneurons are produced together by the final division of common P2 progenitors. During V2a and V2b diversification, Tal1 is necessary and sufficient to promote V2b differentiation and Vsx2 suppresses the expression of motor neuron genes to consolidate V2a interneuron identity. The expression program of Tal1 is triggered by a Foxn4-driven regulatory network in the common P2 progenitors. Why the expression of Tal1 is inhibited in V2a interneurons at the onset of V2a and V2b sub-lineage diversification remains unclear. Since transcription repressor Vsx1 is expressed in the P2 progenitors and newborn V2a cells in zebrafish, we investigated the role of Vsx1 in V2a fate specification during V2a and V2b interneuron diversification in this species by loss and gain-of-function experiments. In <i>vsx1</i> knockdown embryos or knockout Go chimeric embryos, <i>tal1</i> was ectopically expressed in the presumptive V2a cells, while the generation of V2a interneurons was significantly suppressed. By contrast, in <i>vsx1</i> overexpression embryos, normal expression of <i>tal1</i> in the presumptive V2b cells was suppressed, while the generation of V2a interneuron was expanded. Chromatin immunoprecipitation and electrophoretic mobility shift assays in combination with core consensus sequence mutation analysis further revealed that Vsx1 can directly bind to <i>tal1</i> promoter and repress <i>tal1</i> transcription. These results indicate that Vsx1 can directly repress <i>tal1</i> transcription and plays an essential role in defining V2a interneuron sub-lineage during V2a and V2b sub-lineage diversification in zebrafish. |
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| spelling | doaj.art-1a1f36b179c34c54be7a52c2f3cd6f042023-11-20T01:03:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110360010.3390/ijms21103600Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in ZebrafishQi Zhang0Haomang Xu1Wei Zhao2Jianbo Zheng3Lei Sun4Chen Luo5College of Life Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou 310058, ChinaIn the spinal cord, excitatory V2a and inhibitory V2b interneurons are produced together by the final division of common P2 progenitors. During V2a and V2b diversification, Tal1 is necessary and sufficient to promote V2b differentiation and Vsx2 suppresses the expression of motor neuron genes to consolidate V2a interneuron identity. The expression program of Tal1 is triggered by a Foxn4-driven regulatory network in the common P2 progenitors. Why the expression of Tal1 is inhibited in V2a interneurons at the onset of V2a and V2b sub-lineage diversification remains unclear. Since transcription repressor Vsx1 is expressed in the P2 progenitors and newborn V2a cells in zebrafish, we investigated the role of Vsx1 in V2a fate specification during V2a and V2b interneuron diversification in this species by loss and gain-of-function experiments. In <i>vsx1</i> knockdown embryos or knockout Go chimeric embryos, <i>tal1</i> was ectopically expressed in the presumptive V2a cells, while the generation of V2a interneurons was significantly suppressed. By contrast, in <i>vsx1</i> overexpression embryos, normal expression of <i>tal1</i> in the presumptive V2b cells was suppressed, while the generation of V2a interneuron was expanded. Chromatin immunoprecipitation and electrophoretic mobility shift assays in combination with core consensus sequence mutation analysis further revealed that Vsx1 can directly bind to <i>tal1</i> promoter and repress <i>tal1</i> transcription. These results indicate that Vsx1 can directly repress <i>tal1</i> transcription and plays an essential role in defining V2a interneuron sub-lineage during V2a and V2b sub-lineage diversification in zebrafish.https://www.mdpi.com/1422-0067/21/10/3600V2 interneuron diversificationV2a interneuron specificationVsx1Tal1transcriptional repressionspinal cord |
| spellingShingle | Qi Zhang Haomang Xu Wei Zhao Jianbo Zheng Lei Sun Chen Luo Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish International Journal of Molecular Sciences V2 interneuron diversification V2a interneuron specification Vsx1 Tal1 transcriptional repression spinal cord |
| title | Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish |
| title_full | Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish |
| title_fullStr | Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish |
| title_full_unstemmed | Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish |
| title_short | Zygotic Vsx1 Plays a Key Role in Defining V2a Interneuron Sub-Lineage by Directly Repressing <i>tal1</i> Transcription in Zebrafish |
| title_sort | zygotic vsx1 plays a key role in defining v2a interneuron sub lineage by directly repressing i tal1 i transcription in zebrafish |
| topic | V2 interneuron diversification V2a interneuron specification Vsx1 Tal1 transcriptional repression spinal cord |
| url | https://www.mdpi.com/1422-0067/21/10/3600 |
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