Calcium contradictions in cilia

Abstract

A lthough human bodies show left–right symmetry externally, internal organs are asymmetrically located — our heart and stomach, for example, are on the left side of the body. This asymmetry is established at the time when the embryo comprises a flat disc of cells, in which a small pit called the node transiently forms. Each node cell has a primary cilium that rotates clockwise, somehow driving extra cellular fluid from right to left to establish asymmetry 2 . Mounting data 3–5 have supported the idea that cilia on the left of the node directly sense and respond to fluid flow through PKD2 Ca 2+ -channel proteins, which open to produce a left-biased ciliary Ca 2+ signal. Delling and colleagues' evidence that this is not the case could have a profound impact on our understanding of left–right patterning. Debate about how cells in the embryo perceive flow goes back almost 20 years, and several explanatory models have been developed 6 . One posits that a secreted signal-ling molecule called a morphogen becomes enriched on the left side of the node in response to flow. Another argues that vesi-cles containing morphogens travel leftward, delivering their cargo uni laterally. A third, the mechanosensation model, suggests that the leftward force itself is perceived by cilia in crown cells that surround the node. Although no model has been proved or dis-proved, over time, the mechanosensation hypothesis gained the most traction. The authors' cilium-specific Ca