A role for alpha1 tubulin-expressing Müller glia in regeneration of the injured zebrafish retina.

Abstract

Alpha1 tubulin (alpha1T) is a neuron-specific microtubule protein whose expression is induced in the developing and regenerating CNS. In the adult CNS, alpha1T expression remains high in neural progenitors. Transgenic zebrafish harboring a 1.7 kb alpha1T promoter fragment along with the first exon and intron express the transgene in a manner that recapitulates expression of the endogenous gene. We recently showed that this promoter mediates gene induction in retinal ganglion cells during optic nerve regeneration and in a subset of Müller glia that proliferate after retinal injury (Senut et al., 2004). To further characterize these Müller glia, we generated transgenic fish harboring an alpha1T promoter fragment that is specifically induced in these cells after retinal damage. Transgene expression, bromodeoxyuridine (BrdU) labeling, and stem cell marker expression suggested that alpha1T-expressing Müller glia dedifferentiate and become multipotent in response to injury. In addition, green fluorescent protein and BrdU-mediated lineage tracing combined with retinal gene expression analysis indicated that alpha1T-expressing Müller glia were capable of generating retinal neurons and glia. These data strongly suggest alpha1T-expressing Müller glia dedifferentiate and mediate regeneration of the injured zebrafish retina.