RGD Reference Report - Targeted ablation of CRB1 and CRB2 in retinal progenitor cells mimics Leber congenital amaurosis. - Rat Genome Database

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Targeted ablation of CRB1 and CRB2 in retinal progenitor cells mimics Leber congenital amaurosis.

Authors: Pellissier, LP  Alves, CH  Quinn, PM  Vos, RM  Tanimoto, N  Lundvig, DM  Dudok, JJ  Hooibrink, B  Richard, F  Beck, SC  Huber, G  Sothilingam, V  Garcia Garrido, M  Le Bivic, A  Seeliger, MW  Wijnholds, J 
Citation: Pellissier LP, etal., PLoS Genet. 2013 Dec;9(12):e1003976. doi: 10.1371/journal.pgen.1003976. Epub 2013 Dec 5.
RGD ID: 8552784
Pubmed: PMID:24339791   (View Abstract at PubMed)
PMCID: PMC3854796   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pgen.1003976   (Journal Full-text)

Development in the central nervous system is highly dependent on the regulation of the switch from progenitor cell proliferation to differentiation, but the molecular and cellular events controlling this process remain poorly understood. Here, we report that ablation of Crb1 and Crb2 genes results in severe impairment of retinal function, abnormal lamination and thickening of the retina mimicking human Leber congenital amaurosis due to loss of CRB1 function. We show that the levels of CRB1 and CRB2 proteins are crucial for mouse retinal development, as they restrain the proliferation of retinal progenitor cells. The lack of these apical proteins results in altered cell cycle progression and increased number of mitotic cells leading to an increased number of late-born cell types such as rod photoreceptors, bipolar and Muller glia cells in postmitotic retinas. Loss of CRB1 and CRB2 in the retina results in dysregulation of target genes for the Notch1 and YAP/Hippo signaling pathways and increased levels of P120-catenin. Loss of CRB1 and CRB2 result in altered progenitor cell cycle distribution with a decrease in number of late progenitors in G1 and an increase in S and G2/M phase. These findings suggest that CRB1 and CRB2 suppress late progenitor pool expansion by regulating multiple proliferative signaling pathways.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Crb1  (crumbs cell polarity complex component 1)
Crb2  (crumbs cell polarity complex component 2)

Genes (Mus musculus)
Crb1  (crumbs family member 1, photoreceptor morphogenesis associated)
Crb2  (crumbs family member 2)

Genes (Homo sapiens)
CRB1  (crumbs cell polarity complex component 1)
CRB2  (crumbs cell polarity complex component 2)


Additional Information