Study of genetic oscillations of the segmentation clock sheds some light into a disease of the vertebrae

A new study recapitulates in the lab the oscillating patterns of gene expression that coordinate across time and space within a tissue to give rise to the periodic arrangement of the vertebral column.

Oscillations and waves of gene activity are seen in healthy cells. In cells with mutations in genes such as HES7, DLL3, and LFNG, these patterns of gene activity are stopped or disrupted, causing errors in development. Image from: Ebisuya group/EMBL Barcelona.

Mitsuhiro Matsuda, first author of the paper led by Miki Ebisuya at European Molecular Biology Laboratory – Barcelona (EMBL Barcelona) has collaborated with colleagues in several Japanese institutions to recapitulate in vitro the genetic mechanism underlying the periodic structures of our vertebral column.

The expression of this group of genes, known as the segmentation clock, oscillates during embryonic development, with gene activity rising and falling in a regular pattern over time (see movie below). For each oscillation, a new somite – the predecessors of vertebrae and ribs – is formed. Errors in this segmentation clock can cause hereditary disorders of the vertebrae, such as the rare condition spondylocostal dysostosis (SCD).



The researchers created cell lines missing one of the genes known to cause SCD – HES7DLL3 or LFNG – and saw that the genetic oscillations did not happen or did not properly coordinate across the tissue to form the usual travelling waves of gene activity. They then checked the same was true with real patient cells (with DLL3 mutated), and finally used the gene editing tool CRISPR–Cas9 to correct the patient’s mutation, proving that this mutation was responsible for the asynchronisation of the segmentation clock.

You can read more about this study at the EMBL’s website.


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