Researchers have uncovered a novel mechanism they have termed 'developmental stalling', that might explain how errors in the development of human embryos are naturally corrected to prevent birth defects.
|Expression of the Barx1 gene (red) in early tooth development|
In a study published in the journal, Proceedings of the National Academy of Sciences (PNAS), researchers from King's College London's Dental Institute demonstrate how a key developmental pathway, known as the 'BMP pathway' is responsible for ensuring organs correct themselves when growing abnormally in the womb.
Humans are created from a fertilised egg, which develops into an embryo in a process called embryogenesis. The multitude of processes involved in this transition is extremely complex and prone to error. Errors in embryogenesis can lead to birth defects which occur in three to five percent of human births but, given the complexity of embryogenesis, this low figure is in fact surprising.
To explore how potential defects are avoided, the team at King's looked at different shaped teeth in developing mice embryos.
They generated a mutation in a gene called Barx1 that is expressed during the development of molar teeth. However, the loss of Barx1 function did not result in abnormal molars as expected, but rather molar development was 'stalled' by 24 hours during embryogenesis.
This stalling was caused by a reduction in the BMP signalling pathway – a pathway that is already well-established as central to the developing embryo. During this stalling period, the BMP activity then steadily rose to eventually reach levels above the normal threshold, and molar development subsequently accelerated to catch up with the rest of the embryo.