Understanding the genetic control of healthy heart development

Analysing essential but compensatory roles for transcription factors, POU4F1/Brn-3a and POU4F2 Brn-3b in the developing heart using different in-vivo models

Heart defects are the main causes of stillbirths or deaths in newborn babies. However, the causes of such defects are not fully understood. Our genes act like instructions for the development of the heart, but molecular signals are required to switch the right genes on and off at the right time for this process to happen properly. Dr Budhram Mahadeo’s lab has previously identified two related molecules, Brn-3a and Brn-3b, which are involved in controlling genes responsible for normal heart development. However, it is not known exactly how they work, or whether they play similar or opposing roles. In this project, the team will use a gene editing technique, known as CRISPR, to remove one or both of these molecules from zebrafish and mice, and study how this affects heart development at a very early age. This will reveal exactly where and when Brn-3a and Brn-3b function in the developing heart. They will then identify which heart development genes are controlled by one or both of these molecules. This work will help to shed light on the mechanisms that ensure normal heart development. This is essential to understand how this process can go wrong in babies with heart defects.