The tweety Gene Family: From Embryo to Disease

The tweety genes encode gated chloride channels that are found in animals, plants, and even simple eukaryotes, signifying their deep evolutionary origin. In vertebrates, the tweety gene family is highly conserved and consists of three members—ttyh1, ttyh2, and ttyh3—that are important for the regulation of cell volume. While research has elucidated potential physiological functions of ttyh1 in neural stem cell maintenance, proliferation, and filopodia formation during neural development, the roles of ttyh2 and ttyh3 are less characterized, though their expression patterns during embryonic and fetal development suggest potential roles in the development of a wide range of tissues including a role in the immune system in response to pathogen-associated molecules. Additionally, members of the tweety gene family have been implicated in various pathologies including cancers, particularly pediatric brain tumors, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Here, we review the current state of research using information from published articles and open-source databases on the tweety gene family with regard to its structure, evolution, expression during development and adulthood, biochemical and cellular functions, and role in human disease. We also identify promising areas for further research to advance our understanding of this important, yet still understudied, family of genes.