title: p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos.
abstract: BACKGROUND
  Development of the pancreas and the nervous tissues is regulated by common transcription factors. A basic helix-loop-helix protein, p48 of pancreas transcription factor 1 (PTF1), is essential for differentiation of the exocrine acinar cells.
  
  
  RESULTS
  We isolated PTF1 p48 from 9.5-day mouse embryos as a binding protein of RBP-Jkappa, a mediator of Notch signalling. p48 bound to RBP-Jkappa more strongly than and in a distinct way from Notch1. In 9.5-12.5 day embryos, p48 was expressed in the dorsal part of the neural tube as well as in the pancreatic buds. Two lines of evidence suggested functions of p48 in neurogenesis: (i) expression of p48 was induced in P19 cells when they committed to neural fate upon retinoic acid treatment, and (ii) p48 over-expressed in Xenopus embryos repressed the development of neuronal precursors. p48 inhibited the MASH1-activated transcription from the E-box, while p48 stimulated transcription from the PTF1 motif synergistically with E47. The p48/E47-activated transcription from the PTF1 motif was stimulated further by RBP-Jkappa and RBP-Jkappa derivatives that mimicked the active RBP-Jkappa/Notch complex.
  
  
  CONCLUSIONS
  In developing embryos, p48 is expressed in both the nervous system and the pancreas. p48 inhibits neuronal differentiation. We propose possible mechanisms for this inhibition.
authors.affiliation: Division of Gene Function in Animals, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Obata
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: H
authors.initials: H
authors.lastname: Mimura
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.forename: R
authors.initials: R
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Mibu
authors.forename: C
authors.initials: C
authors.lastname: Oka
authors.forename: M
authors.initials: M
authors.lastname: Kawaichi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009420:Nervous System / Q000196:embryology*; D009687:Nuclear Proteins; D010179:Pancreas / Q000254:growth & development; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; C497571:Rbpj protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; C062602:transcription factor PTF1; D008156:Luciferases