Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain
Abstract Background Dbx1 is a homeodomain transcription factor involved in neuronal fate specification belonging to a widely conserved family among bilaterians. In mammals, Dbx1 was proposed to act as a transcriptional repressor by interacting with the Groucho corepressors to allow the specification...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2016-08-01
|
| Series: | EvoDevo |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13227-016-0055-5 |
| _version_ | 1818291387778465792 |
|---|---|
| author | Sonia Karaz Maximilien Courgeon Hélène Lepetit Eugenia Bruno Raimondo Pannone Andrea Tarallo France Thouzé Pierre Kerner Michel Vervoort Frédéric Causeret Alessandra Pierani Giuseppe D’Onofrio |
| author_facet | Sonia Karaz Maximilien Courgeon Hélène Lepetit Eugenia Bruno Raimondo Pannone Andrea Tarallo France Thouzé Pierre Kerner Michel Vervoort Frédéric Causeret Alessandra Pierani Giuseppe D’Onofrio |
| author_sort | Sonia Karaz |
| collection | DOAJ |
| description | Abstract Background Dbx1 is a homeodomain transcription factor involved in neuronal fate specification belonging to a widely conserved family among bilaterians. In mammals, Dbx1 was proposed to act as a transcriptional repressor by interacting with the Groucho corepressors to allow the specification of neurons involved in essential biological functions such as locomotion or breathing. Results Sequence alignments of Dbx1 proteins from different species allowed us to identify two conserved domains related to the Groucho-dependent Engrailed repressor domain (RD), as well as a newly described domain composed of clusterized acidic residues at the C-terminus (Cter) which is present in tetrapods but also several invertebrates. Using a heterologous luciferase assay, we showed that the two putative repressor domains behave as such in a Groucho-dependent manner, whereas the Cter does not bear any intrinsic transcriptional activity. Consistently with in vitro data, we found that both RDs are involved in cell fate specification using in vivo electroporation experiments in the chick spinal cord. Surprisingly, we show that the Cter domain is required for Dbx1 function in vivo, acting as a modulator of its repressive activity and/or imparting specificity. Conclusion Our results strongly suggest that the presence of a Cter domain among tetrapods is essential for Dbx1 to regulate neuronal diversity and, in turn, nervous system complexity. |
| first_indexed | 2024-12-13T02:43:16Z |
| format | Article |
| id | doaj.art-a4a9302d818b487685427f84eea42351 |
| institution | Directory Open Access Journal |
| issn | 2041-9139 |
| language | English |
| last_indexed | 2024-12-13T02:43:16Z |
| publishDate | 2016-08-01 |
| publisher | BMC |
| record_format | Article |
| series | EvoDevo |
| spelling | doaj.art-a4a9302d818b487685427f84eea423512022-12-22T00:02:15ZengBMCEvoDevo2041-91392016-08-017111310.1186/s13227-016-0055-5Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domainSonia Karaz0Maximilien Courgeon1Hélène Lepetit2Eugenia Bruno3Raimondo Pannone4Andrea Tarallo5France Thouzé6Pierre Kerner7Michel Vervoort8Frédéric Causeret9Alessandra Pierani10Giuseppe D’Onofrio11Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéDept. BEOM, Stazione Zoologica A. DohrnDept. BEOM, Stazione Zoologica A. DohrnDept. BEOM, Stazione Zoologica A. DohrnInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéInstitut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris CitéDept. BEOM, Stazione Zoologica A. DohrnAbstract Background Dbx1 is a homeodomain transcription factor involved in neuronal fate specification belonging to a widely conserved family among bilaterians. In mammals, Dbx1 was proposed to act as a transcriptional repressor by interacting with the Groucho corepressors to allow the specification of neurons involved in essential biological functions such as locomotion or breathing. Results Sequence alignments of Dbx1 proteins from different species allowed us to identify two conserved domains related to the Groucho-dependent Engrailed repressor domain (RD), as well as a newly described domain composed of clusterized acidic residues at the C-terminus (Cter) which is present in tetrapods but also several invertebrates. Using a heterologous luciferase assay, we showed that the two putative repressor domains behave as such in a Groucho-dependent manner, whereas the Cter does not bear any intrinsic transcriptional activity. Consistently with in vitro data, we found that both RDs are involved in cell fate specification using in vivo electroporation experiments in the chick spinal cord. Surprisingly, we show that the Cter domain is required for Dbx1 function in vivo, acting as a modulator of its repressive activity and/or imparting specificity. Conclusion Our results strongly suggest that the presence of a Cter domain among tetrapods is essential for Dbx1 to regulate neuronal diversity and, in turn, nervous system complexity.http://link.springer.com/article/10.1186/s13227-016-0055-5Nervous systemSpinal cordNeuronal identityTranscription factorProtein domains |
| spellingShingle | Sonia Karaz Maximilien Courgeon Hélène Lepetit Eugenia Bruno Raimondo Pannone Andrea Tarallo France Thouzé Pierre Kerner Michel Vervoort Frédéric Causeret Alessandra Pierani Giuseppe D’Onofrio Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain EvoDevo Nervous system Spinal cord Neuronal identity Transcription factor Protein domains |
| title | Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain |
| title_full | Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain |
| title_fullStr | Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain |
| title_full_unstemmed | Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain |
| title_short | Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain |
| title_sort | neuronal fate specification by the dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain |
| topic | Nervous system Spinal cord Neuronal identity Transcription factor Protein domains |
| url | http://link.springer.com/article/10.1186/s13227-016-0055-5 |
| work_keys_str_mv | AT soniakaraz neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT maximiliencourgeon neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT helenelepetit neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT eugeniabruno neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT raimondopannone neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT andreatarallo neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT francethouze neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT pierrekerner neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT michelvervoort neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT fredericcauseret neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT alessandrapierani neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain AT giuseppedonofrio neuronalfatespecificationbythedbx1transcriptionfactorislinkedtotheevolutionaryacquisitionofanovelfunctionaldomain |