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 this thesis, we show that ZFP423 interacts functionally and molecularly with the Notch 1 intracellular domain (NICD) in mammalian cell lines and in Xenopus laevis neurula embryos, to activate the expression of the Notchl target Hes5/ESRl. This effect is antagonized by EBF transcription factors, both in cultured cells and in Xenopus laevis embryos, and amplified in vitro by BMP4, the morphogen triggering the activation of SMAD1-SDMAD4 complex.
Taken together, the data presented in this thesis suggest that ZFP423 acts to integrate BMP- and Notch signaling, selectively promoting their convergence onto the Hes5 gene promoter.