Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in the Oa1-/- mouse model of Ocular albinism
Guha, S.; Nguyen, A. M.; Young, A.; Mondell, E.; Farber, D. B.
Show abstract
Mutations in the human Ocular albinism type-1 gene OA1 are associated with abnormal retinal pigment epithelium (RPE) melanogenesis and poor binocular vision resulting from misrouting of ipsilateral retinal ganglion cell (iRGC) axons to the brain. We studied the latter using wild-type (WT) and Oa1-/- mouse eyes. At embryonic stages, the WT RPE-specific Oa1 protein signals through cAMP/Epac1-Erk2-CREB. Following CREB phosphorylation, a pCREB gradient extends from the RPE to the differentiating retinal amacrine and RGCs. In contrast to WT, the Oa1-/- RPE and ventral ciliary-margin-zone, a niche for iRGCs, express less pCREB while their retinas have a disrupted pCREB gradient, indicating Oa1s involvement in pCREB maintenance. Oa1-/- retinas also show hyperproliferation, enlarged nuclei, reduced differentiation, and fewer newborn amacrine and RGCs than WT retinas. Our results demonstrate that Oa1s absence leads to reduced binocular vision through a hyperproliferation-associated block in differentiation that impairs neurogenesis. This may affect iRGC axons routing to the brain.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Dicer loss in Muller glia leads to a defined sequence of pathological events beginning with cone dysfunction 96%
- Genetic and cellular basis of impaired phagocytosis and photoreceptor degeneration in CLN3 disease. 95%
- Topical administration of novel FKBP12 ligand MP-004 improves retinal function and structure in retinitis pigmentosa models. 94%
Similar papers in this journal
- Afadin Sorts Different Retinal Neuron Types into Accurate Cellular Layers 96%
- Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration 95%
- Single cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration 95%
Similar papers in this journal
Similar papers in this journal
- Late gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa 95%
- Tectonic Complex Impedes Diffusion through the Ciliary Transition Zone to Ensure Proper Sorting of Membrane Proteins 94%
- Autophagy disruption and mitochondrial stress precede photoreceptor necroptosis in multiple mouse models of inherited retinal disorders. 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.