Dataset Information

Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar cells by restricting competence.

ABSTRACT: During retinal development, photoreceptors and bipolar cells express the transcription factor Otx2. Blimp1 is transiently expressed in Otx2+ cells. Blimp1 deletion results in excess bipolar cell formation at the expense of photoreceptors. In principle, Blimp1 could be expressed only in Otx2+ cells that are committed to photoreceptor fate. Alternatively, Blimp1 could be expressed broadly in Otx2+ cells and silenced to allow bipolar cell development. To distinguish between these alternatives, we followed the fate of Blimp1 expressing cells using Blimp1-Cre mice and Lox-Stop-Lox reporter strains. We observed that Blimp1+ cells gave rise to all photoreceptors, but also to one third of bipolar cells, consistent with the latter alternative: that Blimp1 inhibits bipolar competence in Otx2+ cells and must be silenced to allow bipolar cell generation. To further test this hypothesis, we looked for transitioning rod photoreceptors in Blimp1 conditional knock-out (CKO) mice carrying the NRL-GFP transgene, which specifically labels rods. Control animals lacked NRL-GFP+ bipolar cells. In contrast, about half of the precociously generated bipolar cells in Blimp1 CKO mice co-expressed GFP, suggesting that rods become re-specified as bipolar cells. Birthdating analyses in control and Blimp1 CKO mice showed that bipolar cells were birthdated as early as E13.5 in Blimp1 CKO mice, five days before this cell type was generated in the wild-type retina. Taken together, our data suggest that early Otx2+ cells upregulate photoreceptor and bipolar genes, existing in a bistable state. Blimp1 likely forms a cross-repressive network with pro-bipolar factors such that the winner of this interaction stabilizes the photoreceptor or bipolar state, respectively.

SUBMITTER: Brzezinski JA

PROVIDER: S-EPMC3845674 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar cells by restricting competence.

Brzezinski Joseph A JA Uoon Park Ko K Reh Thomas A TA

Developmental biology 20131012 2

During retinal development, photoreceptors and bipolar cells express the transcription factor Otx2. Blimp1 is transiently expressed in Otx2+ cells. Blimp1 deletion results in excess bipolar cell formation at the expense of photoreceptors. In principle, Blimp1 could be expressed only in Otx2+ cells that are committed to photoreceptor fate. Alternatively, Blimp1 could be expressed broadly in Otx2+ cells and silenced to allow bipolar cell development. To distinguish between these alternatives, we f ...[more]

PMID: 24125957

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Project description:Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring.SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration.

Dataset Information

Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar cells by restricting competence.

Publications

Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar cells by restricting competence.

Similar Datasets

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