title: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Karaz
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Maximilien
authors.initials: M
authors.lastname: Courgeon
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Lepetit
authors.affiliation: Dept. BEOM, Stazione Zoologica A. Dohrn, Villa Comunale, 80121 Naples, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Bruno
authors.affiliation: Dept. BEOM, Stazione Zoologica A. Dohrn, Villa Comunale, 80121 Naples, Italy.
authors.forename: Raimondo
authors.initials: R
authors.lastname: Pannone
authors.affiliation: Dept. BEOM, Stazione Zoologica A. Dohrn, Villa Comunale, 80121 Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarallo
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: France
authors.initials: F
authors.lastname: Thouzé
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Kerner
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vervoort
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Frédéric
authors.identifier: 0000-0002-0543-4938
authors.initials: F
authors.lastname: Causeret
authors.affiliation: Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pierani
authors.affiliation: Dept. BEOM, Stazione Zoologica A. Dohrn, Villa Comunale, 80121 Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Onofrio
keywords: Nervous system; Neuronal identity; Protein domains; Spinal cord; Transcription factor