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

Aharon Solomon, Yousaf Mian, Cesar Ortega-Cava, Victor Won Tat Liu, Channabasavaiah Basavaraju Gurumurthy, Mayumi Naramura, Vimla Band, Hamid Band

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 Notch1 activation, suggesting an evolutionarily conserved cross-talk between let-7 and the canonical lin-12/Notch signaling pathway.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalDevelopmental Biology
Volume316
Issue number2
DOIs
StatePublished - Apr 15 2008

Keywords

  • Cell fate
  • Developmental timing
  • Heterochronic genes
  • Seam cells
  • let-7
  • lin-12/Notch
  • lin-41
  • microRNA molting

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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