An enhancer located in a Pde6c intron drives transient expression in the cone photoreceptors of developing mouse and human retinas.

How cone photoreceptors are formed during retinal development is only partially known. This is in part because we do not fully understand the gene regulatory network responsible for cone genesis. We reasoned that cis-regulatory elements (enhancers) active in nascent cones would be regulated by the same upstream network that controls cone formation.

Initiation of Otx2 expression in the developing mouse retina requires a unique enhancer and either Ascl1 or Neurog2 activity.

During retinal development, a large subset of progenitors upregulates the transcription factor Otx2, which is required for photoreceptor and bipolar cell formation. How these retinal progenitor cells initially activate Otx2 expression is unclear. To address this, we investigated the cis-regulatory network that controls Otx2 expression in mice.

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3.

Posterior capsule opacification (PCO) is a complication after cataract surgery that can disrupt vision. The epithelial to mesenchymal transition (EMT) of lens epithelial cells (LECs) in response to transforming growth factor β2 (TGFβ2) has been considered an obligatory mechanism for PCO. In this study, we tested the efficacy of aspirin in inhibiting the TGFβ2-mediated EMT of human LECs, LECs in human lens capsular bags, and lensectomized mice.

Transcriptional profiling of murine retinas undergoing semi-synchronous cone photoreceptor differentiation.

Uncovering the gene regulatory networks that control cone photoreceptor formation has been hindered because cones only make up a few percent of the retina and form asynchronously during development. To overcome these limitations, we used a γ-secretase inhibitor, DAPT, to disrupt Notch signaling and force proliferating retinal progenitor cells to rapidly adopt neuronal identity. We treated mouse retinal explants at the peak of cone genesis with DAPT and examined tissues at several time-points by histology and bulk RNA-sequencing.

The Transcription Factor Prdm16 Marks a Single Retinal Ganglion Cell Subtype in the Mouse Retina.

Purpose: Retinal ganglion cells (RGC) can be categorized into roughly 30 distinct subtypes. How these subtypes develop is poorly understood, in part because few unique subtype markers have been characterized. We tested whether the Prdm16 transcription factor is expressed by RGCs as a class or within particular ganglion cell subtypes.

Combinatorial regulation of a Blimp1 (Prdm1) enhancer in the mouse retina.

The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood.

Gsg1, Trnp1, and Tmem215 Mark Subpopulations of Bipolar Interneurons in the Mouse Retina.

Purpose: How retinal bipolar cell interneurons are specified and assigned to specialized subtypes is only partially understood. In part, this is due to a lack of early pan- and subtype-specific bipolar cell markers. To discover these factors, we identified genes that were upregulated in Blimp1 (Prdm1) mutant retinas, which exhibit precocious bipolar cell development.

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

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.