title: Determination of retinal cell fates is affected in the absence of extraocular striated muscles.
abstract: Neural retinas of genetically modified mouse embryos and fetuses entirely lacking extraocular striated muscles (designated as Myf5-/-:MyoD-/- or amyogenic) are used to study in vivo the role of extraocular muscle (i.e., fetal ocular movements) in the genesis of retinal cell diversity. Although retinal lamination and the total number of cells per retinal layer appeared unaffected in amyogenic fetuses, electron microscopy and histochemistry revealed the absence of cholinergic amacrine cell type. By contrast, the amounts of other amacrine cell subpopulations (calretinin-, tyrosine hydroxylase-, and parvalbumin-expressing) were increased, whereas the amounts of Islet1/2-expressing retinal ganglion cells were decreased. Surprisingly, it was not possible to detect any change in proliferation or cell death. Consistently, the number of progenitors for retinal ganglion cells (nestin-expressing precursors) were increased, whereas the amounts of precursors for amacrine cells (syntaxin- and VC1.1-expressing precursors) were decreased in the mutant retinas. The difference in requirements for extraocular muscle support in regulation of precise ratios of retinal neuronal cell types suggests an essential role of extrinsic cues in the determination of retinal cell fates. Taken together, it appears that patterning mechanisms intrinsic to the neural retina specify the basic organization of retinal spatial organization (e.g., retinal layers and total number of cells). However, extrinsic cues seem to change intrinsic properties (e.g., competence) of retinal progenitor cells and influence the ratios of the differentiated cell types (i.e., cell fate choice) they produce.
authors.affiliation: Dalhousie University, Department of Anatomy and Neurobiology, Halifax, Nova Scotia, Canada. bkablar@is.dal.ca
authors.forename: Boris
authors.initials: B
authors.lastname: Kablar
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D025042:Amacrine Cells / Q000201:enzymology / Q000648:ultrastructure; D000818:Animals; D016923:Cell Death; D002455:Cell Division; D048429:Cell Size; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004268:DNA-Binding Proteins; D005133:Eye Movements / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics*; D051787:Myogenic Regulatory Factor 5; D009801:Oculomotor Muscles / Q000002:abnormalities* / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000648:ultrastructure; D013234:Stem Cells / Q000166:cytology; D015534:Trans-Activators
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D015534:Trans-Activators; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase