Atrophin protein RERE positively regulates Notch targets in the developing vertebrate spinal cord. Issue 3 (21st March 2017)

• Record Type: Journal Article
• Authors: Wang, Hui; Gui, Hongxing; Rallo, Michael S.; Xu, Zhiyan; Matise, Michael P.
• Is Part Of: Journal of neurochemistry. Volume 141:Issue 3(2017)
• Page Start: 347
• Page End: 357
• Publication Date: 2017-03-21
• Subjects: Atrophin -- RERE -- Notch -- CBF1 -- NICD; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13969
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: The Notch signaling pathway controls cell fate decision, proliferation, and other biological functions in both vertebrates and invertebrates. Precise regulation of the canonical Notch pathway ensures robustness of the signal throughout development and adult tissue homeostasis. Aberrant Notch signaling results in profound developmental defects and is linked to many human diseases. In this study, we identified the Atrophin family protein RERE (also called Atro2) as a positive regulator of Notch target Hes genes in the developing vertebrate spinal cord. Prior studies have shown that during early embryogenesis in mouse and zebrafish, deficit of RERE causes various patterning defects in multiple organs including the neural tube. Here, we detected the expression of RERE in the developing chick spinal cord, and found that normal RERE activity is needed for proper neural progenitor proliferation and neuronal differentiation possibly by affecting Notch‐mediated Hes expression. In mammalian cells, RERE co‐immunoprecipitates with CBF1 andN otchi ntrac ellulard omain (NICD), and is recruited to nuclear foci formed by over‐expressed NICD1. RERE is also necessary for NICD to activate the expression of Notch target genes. Our findings suggest that RERE stimulates Notch target gene expression by preventing degradation of NICD protein, thereby facilitating the assembly of a transcriptional activating complex containing NICD, CBF1/RBPjκ in vertebrate, Su(H) in Drosophila melanogaster, Lag1 in C. elegans, and other coactivators. Abstract : In the developing spinal cord, Rere regulates neural progenitor proliferation and neuronal differentiation via regulating Notch signaling target Hes expression. In the presence of Rere, NICD is likely to be prevented from proteasome‐mediated degradation, and interact with Rere to form a transcriptional activator complex. Deficient Rere expression reduces Hes5 expression which leads to neural tube defects during early embryogenesis.