ZFIN ID: ZDB-PUB-150204-8
miR-216a regulates snx5, a novel notch signaling pathway component, during zebrafish retinal development
Olena, A.F., Rao, M.B., Thatcher, E.J., Wu, S.Y., Patton, J.G.
Date: 2015
Source: Developmental Biology   400(1): 72-81 (Journal)
Registered Authors: Patton, James G., Thatcher, Elizabeth, Wu, Shu-Yu (Simon)
Keywords: Microrna, Mir-216a, Notch signaling, Retina, Sorting nexin 5, Zebrafish
MeSH Terms:
  • Analysis of Variance
  • Animals
  • Cloning, Molecular
  • DNA Primers/genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology*
  • Gene Knockdown Techniques
  • Image Processing, Computer-Assisted
  • Immunoblotting
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Membrane Proteins/metabolism
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Microarray Analysis
  • Models, Biological
  • Receptors, Notch/metabolism
  • Retina/embryology*
  • Retina/metabolism
  • Signal Transduction/genetics
  • Signal Transduction/physiology*
  • Sorting Nexins/metabolism*
  • Ubiquitin-Protein Ligases/metabolism*
  • Zebrafish/embryology*
  • Zebrafish Proteins/metabolism*
PubMed: 25645681 Full text @ Dev. Biol.
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.