Investigating the bioelectric regulation of pattern formation in Xenopus laevis.
Harris, Hannah L.
- The complex coordination of numerous signals is required to form a fully functional organism. In order for organogenesis to correctly occur, cells must receive both positional information and attain the correct developmental fate. Although the importance of transcription factors in developmental processes is more commonly studied, ion channels have also been shown to play instructive roles during ... read moreembryogenesis. These channels alter the distribution of ions across cellular membranes, generating bioelectric signals that regulate both differentiation and morphogenesis of tissues. We took advantage of the externally developing frog, Xenopus laevis, to further probe the role of bioelectric signaling in development. We investigated the role of one ion channel, hyperpolarization-activated cyclic nucleotide-gated ion channel 4 (HCN4) during embryogenesis. The physiological function of HCN4 as the adult cardiac pacemaker has been well characterized but this channel is expressed before the heart begins to beat, suggesting that it may be important for early patterning events. We provide the first spatio-temporal characterization of the HCN4 expression profile during embryogenesis and reveal a novel role for the channel in coordinating the position of the heart in the body cavity. Reducing channel function via genetic knockdown of the channel induced severely mispatterned cardiac phenotypes and altered the mRNA distribution of critical patterning genes. In addition, we identify a technique, animal cap transplant assays, that gives us both spatial and temporal control over our manipulations, allowing us to carefully assess how bioelectric signals regulate pattern formation. These studies expand what is currently known about how ion channels affect development and highlight the importance of studying novel developmental regulators.read less