How does the embryo know left from right?

At the beginning of gastrulation in the mammal when midline cells of the epiblast begin to move inward to create the primitive groove, a region called the node forms at the anterior end of the groove. Motile cilia at the node create a flow of extracellular fluid across the node. Non-motile nodal cilia are believed to sense the direction of fluid flow across the node. There are two hypotheses about how these cilia function, one chemical and the other mechanical. Both sensory mechanisms are used by cilia elsewhere in the body. In the nose, cilia of the olfactory cells sense chemicals. In the ear, cilia are bent by sound waves, which stimulates ion channels to open. The leftward flow of fluid across the node imposes mechanical forces on the nonmotile cilia that differ on the two sides of the node. Other research, however, supports the possibility of chemical signaling. Research on the mouse node shows that the beating of the cilia causes proteins of a certain size range to form a concentration gradient across the node. More important, it was discovered that nodal cells secrete small vesicles that are swept to the left side of the node by the flow and burst when they contact the nonmotile cilia of surrounding cells. The contents of these vesicles could be the chemical signals that initiate left–right asymmetry in gene expression and development.

Future directions

A major player in the determination of left–right asymmetry is the primary cilium of cells in the node that forms during gastrulation. However, just about every cell in the body has a primary cilium. Up until fairly recently the primary cilia were thought to be vestigial structures or simply organelles to sequester the centriole and thereby inhibit cell division. We now know that the primary cilia of cells function widely in mechanisms of cell signaling and in transduction of physical and chemical stimuli. Just about every organ in the body uses primary cilia for essential functions. Primary cilia have been implicated in many medical conditions such as cancer, kidney disease, obesity, blindness, and developmental disorders. In the near future we will be seeing lots of new discoveries about the functions of primary cilia.