A self-renewing division of zebrafish Muller glial cells generates neuronal progenitors that require N-cadherin to regenerate retinal neurons
- Authors
- Nagashima, M., Barthel, L.K., and Raymond, P.A.
- ID
- ZDB-PUB-131121-8
- Date
- 2013
- Source
- Development (Cambridge, England) 140(22): 4510-4521 (Journal)
- Registered Authors
- Barthel, Linda, Nagashima, Mikiko, Raymond, Pamela
- Keywords
- Muller glia, retinal regeneration, N-cadherin, Alcama
- MeSH Terms
-
- Cadherins/metabolism*
- Asymmetric Cell Division*/drug effects
- Animals
- Cell Dedifferentiation/drug effects
- Heterozygote
- Retinal Ganglion Cells/cytology
- Retinal Ganglion Cells/drug effects
- Retinal Ganglion Cells/metabolism
- Multipotent Stem Cells/cytology
- Multipotent Stem Cells/metabolism
- Zebrafish Proteins/metabolism
- Retinal Neurons/cytology*
- Retinal Neurons/drug effects
- Retinal Neurons/metabolism
- Neurogenesis/drug effects
- Cell Adhesion/drug effects
- Zebrafish/metabolism*
- Models, Biological
- Neural Stem Cells/cytology*
- Neural Stem Cells/drug effects
- Neural Stem Cells/metabolism
- Cell Cycle/drug effects
- Biomarkers/metabolism
- Ouabain/pharmacology
- Regeneration*/drug effects
- Neuroepithelial Cells/cytology
- Neuroepithelial Cells/metabolism
- Ependymoglial Cells/cytology*
- Ependymoglial Cells/drug effects
- Ependymoglial Cells/metabolism
- Photoreceptor Cells, Vertebrate/cytology
- Photoreceptor Cells, Vertebrate/drug effects
- Photoreceptor Cells, Vertebrate/metabolism
- PubMed
- 24154521 Full text @ Development
Müller glia function as retinal stem cells in adult zebrafish. In response to loss of retinal neurons, Müller glia partially dedifferentiate, re-express neuroepithelial markers and re-enter the cell cycle. We show that the immunoglobulin superfamily adhesion molecule Alcama is a novel marker of multipotent retinal stem cells, including injury-induced Müller glia, and that each Müller glial cell divides asymmetrically only once to produce an Alcama-negative, proliferating retinal progenitor. The initial mitotic division of Müller glia involves interkinetic nuclear migration, but mitosis of retinal progenitors occurs in situ. Rapidly dividing retinal progenitors form neurogenic clusters tightly associated with Alcama/N-cadherin-labeled Müller glial radial processes. Genetic suppression of N-cadherin function interferes with basal migration of retinal progenitors and subsequent regeneration of HuC/D+ inner retinal neurons.