PUBLICATION
Conditional gene expression and lineage tracing of tuba1a expressing cells during zebrafish development and retina regeneration
- Authors
- Ramachandran, R., Reifler, A., Parent, J.M., and Goldman, D.
- ID
- ZDB-PUB-101011-21
- Date
- 2010
- Source
- The Journal of comparative neurology 518(20): 4196-4212 (Journal)
- Registered Authors
- Goldman, Dan
- Keywords
- Cre, recombination, neural development, regeneration, retina, Müller glia
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Lineage*
- Gene Expression*
- HEK293 Cells
- Humans
- Promoter Regions, Genetic
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/metabolism
- Recombination, Genetic
- Regeneration/physiology*
- Retina*/cytology
- Retina*/pathology
- Retina*/physiology
- Stem Cells/cytology
- Stem Cells/physiology
- Tubulin*/genetics
- Tubulin*/metabolism
- Zebrafish*/anatomy & histology
- Zebrafish*/genetics
- Zebrafish*/growth & development
- PubMed
- 20878783 Full text @ J. Comp. Neurol.
Citation
Ramachandran, R., Reifler, A., Parent, J.M., and Goldman, D. (2010) Conditional gene expression and lineage tracing of tuba1a expressing cells during zebrafish development and retina regeneration. The Journal of comparative neurology. 518(20):4196-4212.
Abstract
The tuba1a gene encodes a neural-specific α-tubulin isoform whose expression is restricted to the developing and regenerating nervous system. By using zebrafish as a model system for studying CNS regeneration, we recently showed that retinal injury induces tuba1a gene expression in Müller glia that reentered the cell cycle. However, because of the transient nature of tuba1a gene expression during development and regeneration, it was not possible to trace the lineage of the tuba1a-expressing cells with a reporter directly under the control of the tuba1a promoter. To overcome this limitation, we generated tuba1a:CreER(T2) and β-actin2:loxP-mCherrry-loxP-GFP double transgenic fish that allowed us to label tuba1a-expressing cells conditionally and permanently via ligand-induced recombination. During development, recombination revealed transient tuba1a expression in not only neural progenitors but also cells that contribute to skeletal muscle, heart, and intestine. In the adult, recombination revealed tuba1a expression in brain, olfactory neurons, and sensory cells of the lateral line, but not in the retina. After retinal injury, recombination showed tuba1a expression in Müller glia that had reentered the cell cycle, and lineage tracing indicated that these cells are responsible for regenerating retinal neurons and glia. These results suggest that tuba1a-expressing progenitors contribute to multiple cell lineages during development and that tuba1a-expressing Müller glia are retinal progenitors in the adult.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping