Derrick Crawford, Brigham Young University
Life Sciences
Members of the FGF family of signaling factors are key components in distal outgrowth and patterning of the vertebrate limb. These factors are expressed and secreted by the apical ectodermal ridge (AER) on the distal margin of the limb. Blocking their function is known to truncate the limb skeleton. Conversely, replacing the AER with beads soaked in Fgf protein can rescue limb outgrowth and patterning. Our lab has demonstrated that one of the mechanisms whereby the Fgf/AER functions is to mediate directed outgrowth of the adjacent mesenchyme. As the AER regulates growth of mesenchyme toward itself, it would be predicted that the AER’s dimensions would be important for shaping the mesenchyme that it recruits. We have found that the shape of the AER changes over time in a manner that corresponds to the shape of limb elements as they form along the proximal distal axis. Further, mutants that exhibit defects in the dimensions of the AER show corresponding anomalies in the limb skeleton. Given these observations it would be predicted that an Fgf soaked bead being of fixed spherical dimensions would only be capable of forming a cylindrical, rod-shaped limb. A bead placed posteriorly fulfills this expectation whereas a bead placed apically does not. We provide a molecular explanation for this discrepancy. We have also manipulated the shape of the AER surgically and find that similar to beads the shape and the AP position of the AER dictates the shape of the forming limb skeleton.