Possible mechanisms for initiating macroscopic left-right asymmetry in developing organisms

How might systematic left-right (L/R) asymmetry of the body plan originate in multicellular animals (and plants)? Somehow, the microscopic handedness of biological molecules must be brought up to macroscopic scales. Basic symmetry principles suggest that the usual “biological” mechanisms – diffusion and gene regulation – are insufficient to implement the “right-hand rule” defining a third body axis from the other two. Instead, on the cellular level, “physical” mechanisms (forces and collective dynamic states) are needed involving the long stiff fibers of the cytoskeleton. I discuss some possible scenarios; only in the case of vertebrate internal organs is the answer currently known (and even that is in dispute).