Hes7 3′UTR is required for somite segmentation function

Abstract

A set of genes in the posterior end of developing mouse embryos shows oscillatory expression, thereby regulating periodic somite segmentation. Although the mechanism for generating oscillation has extensively been clarified, what regulates the oscillation period is still unclear. We attempted to elongate the oscillation period by increasing the time to transcribe Hes7 in this research. We generated knock-in mice, in which a large intron was inserted into Hes7 3′UTR. The exogenous intron was unexpectedly not properly spliced out and the transcripts were prematurely terminated. Consequently, Hes7 mRNA lost its 3′UTR, thereby reducing the amount of Hes7 protein. Oscillation was damped in the knock-in embryos and periodic somite segmentation does not occur properly. Thus, we demonstrated that Hes7 3′UTR is essential to accumulate adequate amounts of Hes7 protein for the somite segmentation clock that orchestrates periodic somite formation.

Deadenylation by the CCR4‐NOT complex contributes to the turnover of hairy‐related mRNAs in the zebrafish segmentation clock

“…The functional importance of the 3 0 UTR in oscillatory gene expression in the segmentation clock has been described in several species [11,[16][17][18][19][20]. We currently do not know how the 3 0 UTR of these hairyrelated genes mediates distinct turnover rates in the zebrafish PSM.…”

Putative binding sites for mir‐125 family miRNAs in the mouse Lfng 3′UTR affect transcript expression in the segmentation clock, but mir‐125a‐5p is dispensable for normal somitogenesis

“…In the context of segmentation, work done in both chickens and mice demonstrates that the 3 0 untranslated regions (3 0 UTR) of cyclic genes including Hes7 and Lfng promote rapid RNA turnover in the PSM (Hilgers et al, 2005;Nitanda et al, 2014;Fujimuro et al, 2014). 3 0 UTR sequences often influence transcript half-life by providing binding sites for regulatory proteins or small RNAs, and several studies have suggested that regulation of cyclic transcripts by miRNAs could play a critical role in maintenance of stable oscillations (Bonev et al, 2012;Tan et al, 2012;Riley et al, 2013).…”

Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients

“…This lack of coverage represents an issue for ancestral mechanisms such as vertebral segmentation. In mice, it was demonstrated that intronic regions flanking HES7 were critical for this fundamental developmental process 31. In humans, functional intronic variants involved in SDV, such as the TBX6 haplotype located in the 5’ region of the gene, are not covered by WES (online supplementary file S6).…”