PROJECT SUMMARY Human congenital diseases and cancers are major prominent health issues for newborns and adults, respectively. Both types of diseases are closely related to the processes of normal embryonic development, as they share similar aspects, such as, signaling pathways on regulation of differentiation, cell migration, and invasion. Thus, understanding the mechanisms of one system will also shed light on the other. Potassium channels have long been the subject of neuronal and muscular studies, while their roles in embryonic development and cancer remain largely unknown. This is critical for us to better understand disease etiology. The lack of information about the mechanisms of ion channel function in the embryos and in tumors is a significant obstacle to development of targeted therapies for many human congenital diseases and cancers. In this proposal, we will address the demanding need by investigating the inwardly rectifying potassium channels (kir) using newly developed technologies, such as, opto-genetic, chemo-genetic, and genetically encoded voltage and calcium indicators in the zebrafish model system with the two following aims: Aim1. To elucidate how potassium channels and bioelectricity regulate developmental patterning. Aim2. To elucidate oncogenic mechanisms of Kir Channels. The expected outcomes will that we will elucidate a concept-changing mechanism of developmental patterning by ion channels, and identify new oncogenes that could be used as potential targets for cancer therapies. The ion-channel patterning mechanism will not only establish a new concept in developmental biology, but will also provide the foundation for developing prevention or therapeutic strategies for both congenital diseases and cancers.