|ZFIN ID: ZDB-PUB-111027-21|
|Source:||Investigative ophthalmology & visual science 52(12): 8868-77 (Journal)|
|Registered Authors:||Gross, Jeffrey|
|PubMed:||22003118 Full text @ Invest. Ophthalmol. Vis. Sci.|
Purpose: Patched is a well-studied tumor suppressor and negative regulator of the Hedgehog (Hh) pathway. We have previously 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. Here, we extend our analysis of retinal structure and homeostasis in ptc2-/- mutants to juvenile stages to determine if Patched 2 function is required in the post-embryonic eye.
Methods: Histological, immunohistochemical, and molecular analyses were utilized to characterize retinal defects in the 6-week old juvenile ptc2-/- retina.
Results: Juvenile ptc2-/- mutants possess peripheral retinal dysplasias that include the presence of ectopic neuronal clusters in the inner nuclear layer (INL), and regions of disrupted retinal lamination. Retinal dysplasias are locally associated with ectopic proliferation. Through BrdU/EdU labeling and immunohistochemistry assays, we demonstrate that a population of ectopically proliferating cells give rise to the ectopic neuronal clusters in the INL of ptc2-/- mutants, and that this contributes to retinal dysplasia in the mutant eye.
Conclusions: Our 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.