PUBLICATION
NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafish
- Authors
- Ochocinska, M.J., and Hitchcock, P.F.
- ID
- ZDB-PUB-090106-41
- Date
- 2009
- Source
- Mechanisms of Development 126(3-4): 128-141 (Journal)
- Registered Authors
- Hitchcock, Peter
- Keywords
- none
- MeSH Terms
-
- Nerve Tissue Proteins/metabolism*
- Recombinant Fusion Proteins/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Animals
- Neuroglia/cytology
- Neuroglia/drug effects
- Neuroglia/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Oligonucleotides, Antisense/pharmacology
- Embryonic Development/drug effects
- Retina/cytology*
- Retina/drug effects
- Retina/metabolism
- Stem Cells/cytology*
- Stem Cells/drug effects
- Stem Cells/metabolism
- Animals, Genetically Modified
- Cell Proliferation/drug effects
- Basic Helix-Loop-Helix Transcription Factors/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Fertilization/drug effects
- Retinal Rod Photoreceptor Cells/cytology
- Retinal Rod Photoreceptor Cells/drug effects
- Retinal Rod Photoreceptor Cells/metabolism
- Up-Regulation/drug effects
- Mitosis/drug effects
- Cyclins/genetics
- Cyclins/metabolism
- Photoreceptor Cells, Vertebrate/cytology*
- Photoreceptor Cells, Vertebrate/drug effects
- Photoreceptor Cells, Vertebrate/metabolism
- Cell Differentiation/drug effects
- PubMed
- 19121642 Full text @ Mech. Dev.
Citation
Ochocinska, M.J., and Hitchcock, P.F. (2009) NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafish. Mechanisms of Development. 126(3-4):128-141.
Abstract
neuroD is a member of the family of proneural genes, which function to regulate the cell cycle, cell fate determination and cellular differentiation. In the retinas of larval and adult teleosts, neuroD is expressed in two populations of post-mitotic cells, a subset of amacrine cells and nascent cone photoreceptors, and proliferating cells in the lineages that give rise exclusively to rod and cone photoreceptors. Based on previous studies of NeuroD function in vitro and the cellular pattern of neuroD expression in the zebrafish retina, we hypothesized that within the mitotic photoreceptor lineages NeuroD selectively regulates aspects of the cell cycle. To test this hypothesis, gain and loss-of-function approaches were employed, relying on the inducible expression of a NeuroD(EGFP) fusion protein and morpholino oligonucleotides to inhibit protein translation, respectively. Conditional expression of neuroD causes cells to withdraw from the cell cycle, upregulate the expression of the cell cycle inhibitors, p27 and p57, and downregulate the cell cycle progression factors, Cyclin B1, Cyclin D1, and Cyclin E2. In the absence of NeuroD, cells specific for the rod and cone photoreceptor lineage fail to exit the cell cycle, and the number of cells expressing Cyclin D1 is increased. When expression is ectopically induced in multipotent progenitors, neuroD promotes the genesis of rod photoreceptors and inhibits the genesis of Müller glia. These data show that in the teleost retina NeuroD plays a fundamental role in photoreceptor genesis by regulating mechanisms that promote rod and cone progenitors to withdraw from the cell cycle. This is the first in vivo demonstration in the retina of cell cycle regulation by NeuroD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping