Researchers from the Institute for Research in Biomedicine (IRB Barcelona) have revealed that the TLK2 gene is vital for the development of the placenta and for embryo viability in mice. The results are published this week in the journal Cell Death and Differentiation, which belongs to the Nature group.
The placenta, a transient organ that links the developing embryo to its mother, is responsible for nutrient, waste and gas exchange between the foetus and the mother. Despite the difference between embryo development in mice and humans, the finding by IRB Barcelona researchers may be of biomedical relevance. Recent clinical data obtained from a massive genomic analysis of people with intellectual disabilities undertaken in the Netherlands detected mutations in 10 new genes, among them TLK2.
Travis H. Stracker, researcher at IRB Barcelona and head of the study, says, “We propose that mutations in the TLK2 gene in humans could result in impaired placental function during embryo development. Placental defects could result in insufficient oxygen during development and cause neurological disorders.”
Mice depleted of TLK2 produce a smaller embryo and placenta than normal mice; however, the researchers did not observe morphological defects. Defects in the placenta were found to cause embryo death at day 15 of a 20-day gestation period. The scientists detected a reduction in the expression of genes that are crucial for the differentiation of trophoblasts—a group of specialised cells that supply the embryo with nutrients—and that this reduction impairs the function of the placenta.
In the field of cancer, it is known that TLK2 shows increased expression in a subtype of breast tumour and that this increase contributes to cancer progression. Furthermore, TLK1 and TLK2 are involved in cell proliferation, and the activity of these two genes is believed to be necessary for the growth of tumour cells. Given these considerations, both TLK1 and TLK2 may be potential anti-cancer targets.
To address this question, Stracker’s lab, which is devoted to studying the relationship between Genomic Instability and Cancer, is working towards the identification of TLK1 and TLK2 inhibitors in order to examine the function of these genes in models of cancer.
More information on the IRB Barcelona website.