Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal-epithelial-like transition

During the formation of the brain, developing neurons are faced with a logistical problem. After newborn neurons form they must change in shape and move to their final location in the brain. Despite much speculation, little is known about these processes. Neurons mature via the activity of several pathways that control the activity, or expression, of the neuron’s genes. One way of controlling such gene expression is through proteins called transcription factors. At the same time, the developing neurons go through a process called polarization, where different regions of the cell develop different characteristics. However, it was not known how the maturation and polarization processes are linked, or how the developing neurons actively regulate polarization. By studying the developing mouse brain, Singh et al. found that a transcription factor called Zeb1 keeps neurons in a immature state, stopping them from becoming polarized. Further investigation revealed that Zeb1 does this by preventing the production of a group of proteins that helps to polarize the cells. The most common type of malignant brain tumour in children is called a medulloblastoma. Singh et al. analyzed the genes expressed in mice that have a type of medulloblastoma that results from the constant activity of a gene called Sonic Hedgehog in developing neurons. This revealed that these tumour cells contain abnormally high levels of Zeb1, and so do not take on a polarized form. However, artificially restoring other factors that encourage the cells to polarize caused the neurons to mature normally. Further investigation is now needed to find out whether the activity of the Sonic Hedgehog gene regulates Zeb1 activity, and to discover whether inhibiting Zeb1 could prevent brain tumours from developing.