Abstract
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.
Highlights
The first member of the tweety gene family was initially identified in Drosophila melanogaster as a transcriptional unit in the flightless locus and was named after a cartoon character that lacked the ability to fly (Campbell et al, 1993)
Present in most invertebrates as a single gene or one with paralogs, the tweety genes encode chloride channels that are highly conserved in most vertebrates where duplication events resulted in three distinct members, ttyh1–3, each with unique expression patterns (Campbell et al, 2000; Suzuki and Mizuno, 2004; Matthews et al, 2007; Kumada et al, 2010)
RNA-Seq mouse data shows at least low levels of ttyh2 expression in all sampled embryonic and fetal tissues, with highest expression being in the brain or testis/ovaries depending on study and stage (Brown et al, 2015; Papatheodorou et al, 2020)
Summary
The first member of the tweety gene family was initially identified in Drosophila melanogaster as a transcriptional unit in the flightless locus and was named after a cartoon character that lacked the ability to fly (Campbell et al, 1993). A complete understanding of the functional role of tweety family genes requires a thorough analysis of mRNA and protein expression patterns throughout development and beyond.
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