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

作者：Solomon Aharon; Mian Yousaf; Ortega Cava Cesar; Liu Victor Won Tat; Gurumurthy Channabasavaiah Basavaraju; Naramura Mayumi; Band Vimla; Band Hamid^*

来源：Developmental Biology, 2008, 316(2): 191-199.

DOI：10.1016/j.ydbio.2007.12.046

• heterochronic genes
• developmental timing
• lin-12/Notch
• let-7
• lin-41
• microRNA molting
• cell fate
• seam cells

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-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.

• 出版日期2008-4-15
• 单位西北大学