May 8, 2007
In the early 1980s, many scientists thought the enzyme GSK3 had a one-line job description. It helped to activate the enzyme glycogen synthase. But as the years passed, the job description expanded to include a role in determining the developmental fates of certain undifferentiated cells in the embryo. This latter function led a team of scientists to develop a technique a few years ago in which small molecules directly turn GSK3 on and/or off with a high degree of precision at different stages of fetal development. In the March 1 issue of the journal Nature, NIDCR supported scientists and their colleagues used this on-off technique to define in mice the critical developmental period of the palate, or roof of the mouth. Remarkably, the researchers showed that by turning GSK3 back on in pregnant mice during this key developmental window, their embryos in most cases corrected their developing cleft palates. As they reported, five out of nine mouse pups had complete reversal of the cleft, while another newborn had a partial rescue of the cleft. As the authors noted, “New approaches to rescuing selected developmental defects require detailed knowledge of timing and levels of protein expression; our studies provide an improved method for defining these experimental conditions in vivo.”