Several ion channels and transporters are important in left-right patterning (LR). This dissertation summarizes work examining the role of the K_ATP potassium channel in LR, and related projects on the roles of intracellular cytoskeletal cues in LR, an argument for shared origins of LR patterning and planar cell polarity (PCP), and the induction of ectopic eyes by altering levels of potassium channels.

Using loss of function methods, I demonstrate that the K_ATP channel is necessary for LR in Xenopus. It functions during early and mid-cleavage, and randomizes Nodal expression when blocked. I show that K_ATP channel function is necessary for tight junction function. Since tight junctions are important in LR, K_ATP channels may function in LR by regulating tight junctions.

In the next section, we investigate important mechanistic details regarding the function of the H/K-ATPase transporter in LR patterning, and show that it may function with the Kir4.1 channel to cause asymmetric membrane voltage for LR determination. H/K-ATPase is asymmetrically localized in a process dependent on the cytoskeleton. Using molecular motor reporters, we demonstrate that the cytoskeleton of the Xenopus cleavage embryo contains polarity information in all three axes.

The above study suggests that the early embryo is able to compute a consistent relationship between its three axes. We make an argument for LR as a form of planar cell polarity, deriving their polarity from an intracellular chirality.

The second part of the dissertation focuses on a study that arose from an accidental finding: Ectopic eye formation by altering levels of potassium channels. I describe my efforts to characterize this phenomenon.

These studies were motivated by the fascinating roles of bioelectric fields in development. The next steps dissecting the details of the underlying mechanisms will be very interesting, and will provide biomedically-relevant tools with which to control cell fate and tissue development.