Complex Splicing and Neural Expression of Duplicated Tau Genes in Zebrafish Embryos

Abstract

Microtubule-associated protein tau (MAPT) is the major component of the neurofibrillary tangles found in the brains of those suffering from Alzheimer's disease. Various forms of tau lesions are found in other neurodegenerative diseases (tauopathies). We report identification of two MAPT paralogous genes in zebrafish, mapta and maptb, and analysis of their expression patterns during embryonic development. The two paralogues appear to have arisen by duplication of an ancestral teleost MAPT orthologue. Analysis of the splicing of transcripts from both genes during embryogenesis showed that mapta can be spliced into isoforms with between four and six tubulin-binding repeats (4R-6R), while maptb is mainly spliced into 3R isoforms. Expression of both genes is observed predominantly in the developing central nervous system. A particularly large isoform of maptb is specifically expressed in the trigeminal ganglion and in dorsal sensory neurons of the spinal cord. Changes in the subcellular ratio of 3R and 4R isoforms can have pathological consequences in mammals. The predominant production of 4R-6R isoforms from mapta and of 3R isoforms from maptb suggests that zebrafish embryos will be a useful tool with which to study the discrete functions and interactions of the 3R and 4R MAPT isoforms.