title: Ectopic proliferation contributes to retinal dysplasia in the juvenile zebrafish patched2 mutant eye.
abstract: OBJECTIVE
  Patched is a well-studied tumor suppressor and negative regulator of the Hedgehog (Hh) pathway. Earlier work in this laboratory has shown that embryonic zebrafish patched2 (ptc2) mutant retinas possess an expanded ciliary marginal zone (CMZ) and phenotypes similar to those in human patients with basal cell naevus syndrome (BCNS), a congenital disorder linked to mutations in the human PTCH gene. This study extends the analysis of retinal structure and homeostasis in ptc2-/- mutants to juvenile stages, to determine whether Patched 2 function is essential in the postembryonic eye.
  
  
  METHODS
  Histologic, immunohistochemical, and molecular analyses were used to characterize retinal defects in the 6-week-old juvenile ptc2-/- retina.
  
  
  RESULTS
  Juvenile ptc2-/- mutants exhibited peripheral retinal dysplasias that included the presence of ectopic neuronal clusters in the inner nuclear layer (INL) and regions of disrupted retinal lamination. Retinal dysplasias were locally associated with ectopic proliferation. BrdU/EdU labeling and immunohistochemistry assays demonstrated that a population of ectopically proliferating cells gave rise to the ectopic neuronal clusters in the INL of ptc2-/- mutants and that this contributed to retinal dysplasia in the mutant eye.
  
  
  CONCLUSIONS
  These results demonstrate a direct link between overproliferation and retinal dysplasia in the ptc2-/- juvenile retina and establish ectopic proliferation as the likely cellular underpinning of retinal dysplasia in juvenile ptc2-/- mutants.
authors: Section of Molecular Cell and Developmental Biology, The University of Texas at Austin, Austin, Texas, USA.
authors: Jonathan
authors: J
authors: Bibliowicz
authors: Jeffrey M
authors: JM
authors: Gross
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002828:Choristoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D012160:Retina / Q000002:abnormalities* / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D015792:Retinal Dysplasia / Q000235:genetics* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D029961:Zebrafish Proteins; C491715:ptch1 protein, zebrafish; D049452:Green Fluorescent Proteins