For the first time a study reveals the fundamental role of the TLK2 gene in the embryonic development of mice. Despite the differences in this stage between rodents and humans, this finding could have biomedical relevance.

The placenta is an ephemeral organ that links the developing embryo to the mother, to meet the needs of breathing, nutrition and expulsion of the fetus. Scientists from the Biomedical Research Institute (IRB Barcelona) reveal that TLK2 gene is indispensable for the development of the placenta and embryo viability in mice. The results are published today in the Nature’s journal Cell Death and Differentiation.

In mice without TLK2, the placenta and the embryo are smaller, but the researchers do not observe morphological defects in the embryo. By the day 15 to 20 of gestation, the embryo dies caused by failures in the placenta.

Scientists detect a reduction in the expression of genes important for the proliferation or survival of trophoblasts –a group of specialized cells that provide nutrients to the embryo– with effects on the functionality of the placenta.

Dispensable in adults

In this same work, scientists also reveal that TLK2 is, however, completely dispensable in adult mice. Its function is supplemented by its “twin” gene, TLK1. The absence of either gene is offset by the presence of the other, and the animals are apparently normal, healthy and have the same life expectancy.

“Only when we eliminate the two genes at once we do see problems of genomic instability, chromosome segregation and complications of this kind,” summarizes doctoral student at IRB Barcelona, Sandra Segura-Bayona, the study’s first author along with postdoctoral researchers Philip Knobel and Helena Gonzalez Burón.

The researchers conclude that both genes maintain genomic integrity and cell viability and that their functions in adults are redundant.

TLK1 and TLK2 in cancer

In the cancer section, TLK2 is known to be increased in a breast tumor subtype, and such increase is involved in the progression of cancer.

In addition, it is known that both TLK1 and TLK2 are involved in cell proliferation, and such activity is necessary for the progression of tumor cells. From this knowledge, it is speculated that both TLK1 and TLK2 could be targets of anti-cancer therapies.

In order to advance in this line, the laboratory of Travis H. Stracke –which dedicated to study the relationship between Genomic Instability and Cancer– is developing inhibitors of TLK1 and TLK2 to study the functions of these genes in animal models of cancer.

Despite the differences between the embryonic development of mice and humans, this finding could have biomedical relevance. This gene was recently associated, through a massive genomic analysis developed in the Netherlands, with intellectually disabled people, among whom 10 new genes were detected, including TLK2.

 

Source: SINC