The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

In mammals, the brain and spinal cord develop from a flat sheet of cells called the neural plate, which bends around to create a structure known as the neural tube. This bending process occurs through a complex sequence of cell shape changes. The cells in the neural plate are initially short and wide, but transform into long, thin cells as the neural plate forms. Problems that prevent the neural tube from forming correctly are amongst the most common birth defects in humans. Many cancer cells contain a mutation that affects a gene that produces a protein called PTEN. This protein normally activates a tumor suppressor pathway, and so cancer cells that lack PTEN divide and grow uncontrollably. Grego-Bessa et al. have now examined mouse embryos that lack this gene, and found that the neural plate in such embryos forms irregular ruffles rather than a closed tube. Further investigation revealed that the neural tube defects are not due to the inactivation of the traditional tumor suppressor pathway. Instead, correct neural tube formation relies upon the ability of PTEN to remove phosphate groups from a target lipid, which is important for limiting the activity of an enzyme called PDK1. Unlimited PDK1 activity causes complex changes that prevent the neural plate cells from elongating and packing together correctly. Future work is now needed to investigate the exact molecules targeted by PDK1 and the roles they play in disorders and diseases caused by a lack of the PTEN protein.