p48 subunit of mouse PTF1 binds to RBP-J kappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos

Background: Development of the pancreas and the nervous tissues is regulate d by common transcription factors. A basic helix-loop-helix protein, p48 of pancreas transcription factor 1 (PTF1), is essential for differentiation o f the exocrine acinar cells. Results: We isolated PTF1 p48 from 9.5-day mouse embryos as a binding prote in of RBP-J kappa, a mediator of Notch signalling. p48 bound to RBP-J kappa more strongly than and in a distinct way from Notch1. In 9.5-12.5 day embr yos, 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 ne urogenesis: (i) expression of p48 was induced in P19 cells when they commit ted to neural fate upon retinoic acid treatment, and (ii) p48 over-expresse d in Xenopus embryos repressed the development of neuronal precursors. p48 inhibited the MASH1-activated transcription from the E-box, while p48 stimu lated transcription from the PTF1 motif synergistically with E47. The p48/E 47-activated transcription from the PTF1 motif was stimulated further by RB P-J kappa and RBP-J kappa derivatives that mimicked the active RBP-J kappa /Notch complex. Conclusions: In developing embryos, p48 is expressed in both the nervous sy stem and the pancreas. p48 inhibits neuronal differentiation. We propose po ssible mechanisms for this inhibition.