Skip to main content
eScholarship
Open Access Publications from the University of California

MiR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability

  • Author(s): Parchem, RJ
  • Parchem, RJ
  • Moore, N
  • Moore, N
  • Fish, JL
  • Parchem, JG
  • Braga, TT
  • Braga, TT
  • Shenoy, A
  • Shenoy, A
  • Oldham, MC
  • Oldham, MC
  • Rubenstein, JLR
  • Schneider, RA
  • Blelloch, R
  • Blelloch, R
  • et al.

Published Web Location

http://www.sciencedirect.com/science/article/pii/S2211124715007123
No data is associated with this publication.
Abstract

© 2015 The Authors. The evolutionarily conserved miR-302 family of microRNAs is expressed during early mammalian embryonic development. Here, we report that deletion of miR-302a-d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout embryos have an anterior neural tube closure defect associated with a thickened neuroepithelium. The neuroepithelium shows increased progenitor proliferation, decreased cell death, and precocious neuronal differentiation. mRNA profiling at multiple time points during neurulation uncovers a complex pattern of changing targets over time. Overexpression of one of these targets, Fgf15, in the neuroepithelium ofthe chick embryo induces precocious neuronal differentiation. Compound mutants between mir-302 and the related mir-290 locus have a synthetic lethal phenotype prior to neurulation. Our results show that mir-302 helps regulate neurulation by suppressing neural progenitor expansion and precocious differentiation. Furthermore, these results uncover redundant roles for mir-290 and mir-302 early in development. Using a knockout mouse model, Parchem etal. demonstrate that miR-302-knockout embryos have defects in proliferation, cell death, and differentiation during early neural development that prevent neural tube closure. They systematically identify misregulated targets during development and show that the related miR-290 cluster is functionally redundant with miR-302 at early stages.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item