Upregulation of the let-7 microRNA with precocious development in lin-12/Notch hypermorphic Caenorhabditis elegans mutants

Dev Biol. 2008 Apr 15;316(2):191-9. doi: 10.1016/j.ydbio.2007.12.046. Epub 2008 Jan 11.

Abstract

The lin-12/Notch signaling pathway is conserved from worms to humans and is a master regulator of metazoan development. Here, we demonstrate that lin-12/Notch gain-of-function (gf) animals display precocious alae at the L4 larval stage with a significant increase in let-7 expression levels. Furthermore, lin-12(gf) animals display a precocious and higher level of let-7 gfp transgene expression in seam cells at L3 stage. Interestingly, lin-12(gf) mutant rescued the lethal phenotype of let-7 mutants similar to other known heterochronic mutants. We propose that lin-12/Notch signaling pathway functions in late developmental timing, upstream of or in parallel to the let-7 heterochronic pathway. Importantly, the human microRNA let-7a was also upregulated in various human cell lines in response to Notch 1 activation, suggesting an evolutionarily conserved cross-talk between let-7 and the canonical lin-12/Notch signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blotting, Northern
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Larva
  • MicroRNAs / genetics*
  • Mutation*
  • Phenotype
  • Receptors, Notch / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MicroRNAs
  • Receptors, Notch
  • let-7 microRNA, C elegans
  • Green Fluorescent Proteins

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