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Title: ZFP423 coordinates Notch pathway, Bmp signaling and EBF/COE transcription factors to regulate Hes5 gene expression
Author: Masserdotti, Giacomo
ISNI:       0000 0004 2694 8692
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2010
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral