miR-216a regulates snx5, a novel notch signaling pathway component, during zebrafish retinal development.

Olena AF, Rao MB, Thatcher EJ, Wu SY, Patton JG
Dev Biol. 2015 400 (1): 72-81

PMID: 25645681 · PMCID: PMC4361363 · DOI:10.1016/j.ydbio.2015.01.016

Precise regulation of Notch signaling is essential for normal vertebrate development. Mind bomb (Mib) is a ubiquitin ligase that is required for activation of Notch by Notch׳s ligand, Delta. Sorting Nexin 5 (SNX5) co-localizes with Mib and Delta complexes and has been shown to directly bind to Mib. We show that microRNA-216a (miR-216a) is expressed in the retina during early development and regulates snx5 to precisely regulate Notch signaling. miR-216a and snx5 have complementary expression patterns. Knocking down miR-216a and/or overexpression of snx5 resulted in increased Notch activation. Conversely, knocking down snx5 and/or miR-216a overexpression caused a decrease in Notch activation. We propose a model in which SNX5, precisely controlled by miR-216a, is a vital partner of Mib in promoting endocytosis of Delta and subsequent activation of Notch signaling.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (22)

Analysis of Variance Animals Cloning, Molecular DNA Primers Gene Expression Profiling Gene Expression Regulation, Developmental Gene Knockdown Techniques Image Processing, Computer-Assisted Immunoblotting In Situ Hybridization Intracellular Signaling Peptides and Proteins Membrane Proteins Microarray Analysis MicroRNAs Models, Biological Receptors, Notch Retina Signal Transduction Sorting Nexins Ubiquitin-Protein Ligases Zebrafish Zebrafish Proteins

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