In utero protein regulation
A novel strategy for regulating a protein important in development is described online in Nature this week. Michael T. Longaker and colleagues report that, in mice, glycogen synthase kinase-3beta (GSK-3beta) can be artificially controlled from within the mother's uterus, in a reversible and time-controlled manner.GSK-3beta plays an integral part in a variety of biological processes, although its specific developmental roles remain unclear. In the present study the authors used an existing chemically regulated form of the GSK-3beta gene, whereby expression of the GSK-3beta protein is controlled by the presence or absence of the drug rapamycin. Using this approach combined with conventional mutant analysis they defined a specific requirement for GSK-3beta in midline development: mice that did not express the protein had cleft palate, incomplete fusion of the ribs and a split sternum.In addition, the authors were able to rescue some of the developmental defects using maternal rapamycin treatment to restore internal GSK-3beta activity during two distinct windows of gestation. They propose that their studies provide an improved method for defining the timing and level of protein expression during development, a detailed knowledge of which is essential for rescuing developmental defects.Author contact:Michael T. Longaker (Stanford University Medical Center, CA, USA)Tel: +1 650 736 1707; E-mail: longaker@stanford.edu