دورية أكاديمية
Tlx3 Exerts Direct Control in Specifying Excitatory Over Inhibitory Neurons in the Dorsal Spinal Cord
| العنوان: | Tlx3 Exerts Direct Control in Specifying Excitatory Over Inhibitory Neurons in the Dorsal Spinal Cord |
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| المؤلفون: | Monteiro, FA, Miranda, RM, Samina, MC, Dias, AF, Raposo, AASF, Oliveira, P, Reguenga, C, Castro, DS, Lima, D |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | Frontiers Media |
| سنة النشر: | 2021 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| مصطلحات موضوعية: | Chromatin immunoprecipitation, Dorsal horn, Excitatory neuron, Spinal cord, T-cell leukemia homeobox 3 |
| الوصف: | The spinal cord dorsal horn is a major station for integration and relay of somatosensory information and comprises both excitatory and inhibitory neuronal populations. The homeobox gene Tlx3 acts as a selector gene to control the development of late-born excitatory (dILB) neurons by specifying glutamatergic transmitter fate in dorsal spinal cord. However, since Tlx3 direct transcriptional targets remain largely unknown, it remains to be uncovered how Tlx3 functions to promote excitatory cell fate. Here we combined a genomics approach based on chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and expression profiling, with validation experiments in Tlx3 null embryos, to characterize the transcriptional program of Tlx3 in mouse embryonic dorsal spinal cord. We found most dILB neuron specific genes previously identified to be directly activated by Tlx3. Surprisingly, we found Tlx3 also directly represses many genes associated with the alternative inhibitory dILA neuronal fate. In both cases, direct targets include transcription factors and terminal differentiation genes, showing that Tlx3 directly controls cell identity at distinct levels. Our findings provide a molecular frame for the master regulatory role of Tlx3 in developing glutamatergic dILB neurons. In addition, they suggest a novel function for Tlx3 as direct repressor of GABAergic dILA identity, pointing to how generation of the two alternative cell fates being tightly coupled. ; This work is a result of the project Norte-01-0145-FEDER-000008 – Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work was also supported by FCT – Fundação para a Ciência e Tecnologia (Grants PTDC/SAU-OBD/099886/2008 to DL and PTDC/NEU-NMC/0315/2012 to DC) and Universidade do Porto/Banco Santander Totta (Projetos Pluridisciplinares to FM). We ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2296-634X |
| العلاقة: | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-OBD%2F099886%2F2008/PT; info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FNEU-NMC%2F0315%2F2012/PT; Frontiers in Cell and Developmental Biology, vol.9:642697; https://www.frontiersin.org/articles/10.3389/fcell.2021.642697/fullTest; https://hdl.handle.net/10216/152496Test |
| DOI: | 10.3389/fcell.2021.642697 |
| الإتاحة: | https://doi.org/10.3389/fcell.2021.642697Test https://hdl.handle.net/10216/152496Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BA9CA1D4 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2296634X |
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| DOI: | 10.3389/fcell.2021.642697 |