Cilia in Left-Right Development
Discovery of intraciliary calcium oscillations in the zebrafish node. Yuan et al. (2016).
Our lab researches the two types of cilia found in the LRO (Left Right Organizer) that play key roles in creating the vertebrate LR axis. Dynein-driven motile cilia generate directional flow of extraembryonic fluid across the LRO, termed “nodal flow”. Sensory primary cilia on the peripheries of the LRO detect this flow and trigger calcium signaling, leading to asymmetric degradation of the BMP antagonist Dand5 on the left side of the LRO. Since Dand5 works as an inhibitor of Nodal, its degradation allows Nodal signaling to propagate and ultimately result in the proper LR axis.
Previously we have shown that Polycystin-2 (Pkd2), a calcium channel protein, is highly localized to a subset of primary cilia in the LRO. Mice with LoF mutations affecting Pkd2 have abnormal LR asymmetry. Together, this data suggests that embryonic cilia may be required to both create and sense nodal flow.
We are interested in how the asymmetric calcium signal is transduced to asymmetric Nodal expression in the developing embryo in order to set up the LR axis.
Selected Publications: