Zinc finger protein 423 encodes a 30 Zn-finger transcription factor involved in cerebellar and olfactory development. ZFP423 is a known interactor of SMAD1-SMAD4 and of Collier/Olf-1/EBF proteins, and acts as a modifier of retinoic acid-induced differentiation. In the present article, we show that ZFP423 interacts with the Notch1 intracellular domain in mammalian cell lines and in Xenopus neurula embryos, to activate the expression of the Notch1 target Hes5/ESR1. This effect is antagonized by EBF transcription factors, both in cultured cells and in Xenopus embryos, and amplified in vitro by BMP4, suggesting that ZFP423 acts to integrate BMP and Notch signaling, selectively promoting their convergence onto the Hes5 gene promoter.
This work was supported, in whole or in part, by National Institutes of Health Grant EY012274 (to M. L. V.). This work was also supported by the EU consortium contract EuroSyStem (to G. G. C.) and the Fondazione CARIPLO (Network Operativo per la Biomedicina di Eccellenza in Lombardia), from the Italian Ministry of University and Research (MIUR-PRIN 2007).
