Does DAC GTPase Play a Role in EPHA4 Signaling in Xenopus Embryos?
In embryonic development, many cells migrate in order to correctly form new structures. One way that guidance of this migration occurs is via a repulsion mechanism involving the Eph family of receptors. Signaling through these receptors activates the repulsive mechanism that limits which tissues can interact with each other. The repulsion mechanism is not well understood, but involves the reorganization of the actin cytoskeleton and a loss of cell-cell adhesion. Activation of the EphA4 signaling pathway in Xenopus laevis embryos has been shown to cause the repulsion mechanism. The Rho family of GTPases consisting of Cdc42, Rho, and Rac, has been linked to the reorganization of the actin cytoskeleton and Rho has been demonstrated to be part of the EphA4 pathway. The present study tested the hypothesis that a related GTPase, Rac, is also part of EphA4 signaling. This was done by expressing mutant forms of Rac in Xenopus laevis embryos and assessing whether they mimicked the effects of EphA4 signaling. As the concentration of RNA coding for constitutively active Rac increased, the degree of cellular dissociation also increased indicating possible EphA4 activity. However, when embryos were injected with the dominant negative form of Rac RNA to prevent cellular dissociation caused by the receptor-ligand, EPP+TGFα, no rescue was observed.