Shapes of Things: The Control of Morphogenesis by the Actin Skeleton
The shape of the embryo, and the shapes of its constituent organs, are controlled by the changing shapes and movements of its cells. In turn, shape and movement of cells in the embryo are controlled by the actin skeleton.
In this NIH-funded project we study the control of actin assembly during morphogenesis, using the early Xenopus embryo as a model. We have found that at the blastula stage, actin assembly in the cortex of each cell is controlled by the amount of the cell adhesion protein C-cadherin expressed on the surface (Tao et al. 2007). Cadherin expression is in turn controlled by G protein-coupled signaling pathways (Tao et al. 2005, Lloyd et al. 2005). In the absence of this actin assembly pathway caused embryo collapse and loss of shape.
At the neurula stage, new cadherins are expressed; N-cadherin in the neural plate and E-cadherin in the presumptive epidermis. We have shown that these also control cortical actin assembly in their respective tissues, and when they are depleted using antisense morpholino oligos, the characteristic morphogenetic movements of the neural plate and presumptive epidermis do not take place (Nandadasa et al. 2009).
The time-lapse movie below shows two sibling Xenopus leavis embryos undergoing neurulation. The embryo in left is an uninjected control, the embryo in right has been depleted of N-cadherin protein in the neural plate using an antisense morpholino. In the N-cadherin depleted embryo, the neural plate fails to undergo invagination and remains open. Due to the pushing forces applied by the unaffected non-neural ectoderm, a distinct lip like structure appears surrounding the N-cadherin depleted neural plate.
Click here to view movie:
N-cad MO Neurulation MovieThese studies show that cadherin-based actin assembly is essential for the generation of shape of the whole embryos, and of its early organs. We are now studying the molecular mechanisms of cadherin expression and actin assembly in the model systems we have established. These studies may have implications for our understanding of congenital disorders of infancy. Spinal bifida, for examp le, is caused by a failure of morphogenetic movements of the neural plate very similar to that seen when N-cadherin is depleted in the early Xenopus embryo. Defects in cadherin-based actin assembly may well underlie disorders of morphogenetic movements during human development also.
