Mir-125a-5p-mediated regulation of Lfng is essential for the avian segmentation clock

Somites are embryonic precursors of the axial skeleton and skeletal muscles and establish the segmental vertebrate body plan. Somitogenesis is controlled in part by a segmentation clock that requires oscillatory expression of genes including Lunatic fringe (Lfng). Oscillatory genes must be tightly regulated at both the transcriptional and posttranscriptional levels for proper clock function. Here, we demonstrate that microRNA-mediated regulation of Lfng is essential for proper segmentation during chick somitogenesis. We find that mir-125a-5p targets evolutionarily conserved sequences in the Lfng 3' UTR and that preventing interactions between mir-125a-5p and Lfng transcripts in vivo causes abnormal segmentation and perturbs clock activity. This provides strong evidence that microRNAs function in the posttranscriptional regulation of oscillatory genes in the segmentation clock. Further, this demonstrates that the relatively subtle effects of microRNAs on target genes can have broad effects in developmental situations that have critical requirements for tight posttranscriptional regulation.