title: Impaired retinal differentiation and maintenance in zebrafish laminin mutants.
abstract: OBJECTIVE
  To characterize morphologic and physiological alterations in the retina of three laminin mutant zebrafish, bashful (bal, lama1), grumpy (gup, lamb1), and sleepy (sly, lamc1), which were identified in forward genetic screens and were found to be impaired in visual functions.
  
  
  METHODS
  Mutant larvae were observed for defects in visual behavior by testing their optokinetic response (OKR). In addition, electroretinograms (ERG) were measured and retinal morphology was examined by standard histology, immunocytochemistry, TUNEL assay, and electron microscopy.
  
  
  RESULTS
  Both, gup and sly showed no OKR at any light intensity tested, whereas bal embryos showed some remaining OKR behavior at more than 40% of contrast. Consistent with the OKR result, gup and sly did not show an ERG response at any light intensity tested, whereas bal mutants exhibited small a- and b-waves at high light intensities. All three laminin mutants showed altered ganglion cell layers, optic nerve fasciculations, and lens defects. Again, bal showed the least severe morphologic phenotype with no additional defects. In contrast, both, gup and sly, showed severe photoreceptor outer segment shortening and synapse alteration (floating ribbons) as well as increased cell death.
  
  
  CONCLUSIONS
  Lamb1 and lamc1 chains play an important role in the morphogenesis of photoreceptors and their synapses. In contrast, lama1 is not involved in outer retina development.
authors.affiliation: Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, Switzerland. biehlmaier@hifo.unizh.ch
authors.forename: Oliver
authors.initials: O
authors.lastname: Biehlmaier
authors.forename: Yuri
authors.initials: Y
authors.lastname: Makhankov
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004596:Electroretinography; D004625:Embryo, Nonmammalian / Q000473:pathology*; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000235:genetics*; D007908:Lens, Crystalline / Q000196:embryology / Q000473:pathology; D008856:Microscopy, Fluorescence; D009024:Morphogenesis; D009154:Mutation; D017120:Nystagmus, Optokinetic; D009900:Optic Nerve / Q000196:embryology / Q000473:pathology; D012160:Retina / Q000196:embryology* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D007797:Laminin; D029961:Zebrafish Proteins; C462526:lamb1a protein, zebrafish; C462527:lamc1 protein, zebrafish; C510925:laminin alpha1, zebrafish