Scientists find the genetic code underlying limb growth

By Sally Robertson, B.Sc.Sep 18 2018

Researchers at the Ecole Polytechnique Fédérale de Lausanne have discovered the gene code that sets the pace and order of fetal development.

Sebastian Kaulitzki | Shutterstock

Scientists already knew that genes called Hoxd genes are involved in the development of the body, but most studies have only looked at the entire tissues of developing organs.

This new study, which has recently been published in BMC Biology, analysed development at the single-cell level and has provided a higher-resolution picture of how Hoxd genes control development.

By studying the maturation of paws and digits in mice, Pierre Fabre and colleagues have found that a combination of Hoxd genes is essential to the developmental cascade.

The team used a single-cell RNA sequencing technique to study the expression pattern of thousands of developmental genes that are active within single progenitor cells – cells that are just one stage more specialized than stem cells.

The researchers found that 343 genes within each cell are associated with specific cellular states, many of which play a role in the packaging and arrangement of DNA, as well as the expression patterns that lead to the development of the paw’s digits.

The team identified a select set of six combinations of five Hoxd genes involved in the development of digits. Each of the combinations involves one, two or four Hoxd genes, with the most simple (one gene) occurring at the beginning of development and the most complex combination (four genes) occurring at the later stages of development.

Fabre says the research has demonstrated how architect genes act in concert, following a gradual progression in every developing cell to produce our fully matured arms and hands at the right time and the right place:

"The Hoxd gene combinations provide a machinery that generate a spectrum of functionally different cells within genetically-defined classes of limb patterning motifs. This will pave the way for future genetic work to understand how cells get to synchronize the combined activation of multiple genes."