title: A self-renewing division of zebrafish Müller glial cells generates neuronal progenitors that require N-cadherin to regenerate retinal neurons.
abstract: 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.
authors.affiliation: Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nagashima
authors.forename: Linda K
authors.initials: LK
authors.lastname: Barthel
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Raymond
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D054337:Cell Dedifferentiation / Q000187:drug effects; D063928:Ependymoglial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006579:Heterozygote; D008954:Models, Biological; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055351:Retinal Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; C513786:N-cadherin, zebrafish; D029961:Zebrafish Proteins; D010042:Ouabain
keywords: Alcama; Müller glia; N-cadherin; Retinal regeneration