Mapping membrane lipids in the developing and adult mouse retina under physiological and pathological conditions using mass spectrometry.

Membrane phospholipids play pivotal roles in various cellular processes, and their levels are tightly regulated. In the retina, phospholipids had been scrutinized because of their distinct composition and requirement in visual transduction. However, how lipid composition changes during retinal development remains unclear.

RasV12 Expression in Microglia Initiates Retinal Inflammation and Induces Photoreceptor Degeneration.

Purpose: The role of activated retinal microglia in driving retinal degeneration has been implicated in a number of in vivo disease models. Here, we investigated the primary consequences of microglial activation by the specific expression of constitutively active Ras in microglia in a transgenic mouse model before the onset of any degenerative changes in the retina.

Methods: The double transgenic lines CAG-LSL-RasV12-IRES-EGFP; Cx3cr1CreER/+ (Cx3cr1-RasV12 mice) and CAG-LSL-EGFP; Cx3cr1CreER_+ (control mice) were generated.

Apigenin Regulates Activation of Microglia and Counteracts Retinal Degeneration.

Photoreceptor degeneration is a major cause of blindness. Microglia are known to play key roles in the pathogenesis and progression of neural degeneration. We examined the possible use of apigenin, which is a naturally occurring flavonoid, for the treatment of photoreceptor degeneration through regulation of microglial activities.

H3K27me3 demethylase UTX regulates the differentiation of a subset of bipolar cells in the mouse retina.

Di- and trimethylation of lysine 27 on histone 3 (H3K27me2/3) is a critical gene repression mechanism. We previously showed that down-regulation of the H3K27 demethylase, Jumonji domain-containing protein 3 (JMJD3), resulted in a reduced number of protein kinase C (PKC)α-positive rod ON-bipolar cells. In this work, we focused on the role of another H3K27 demethylase, ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX), in retinal development.

Ras activation in retinal progenitor cells induces tumor formation in the eye.

The RAS gene family members, H-RAS, K-RAS, and N-RAS, are frequently mutated in human cancer. A subset of retinal tumors displays K-RAS mutations; however, the specific role of RAS activation on retinal tumor formation is unclear. To examine the role of RAS in retinal development, we overexpressed the mutant H-RAS gene (G12V) in retinal progenitor cells (RPCs), a multipotent progenitor cell population that gives rise to all six neuron types in the retina and to the Muller glia.

Forkhead Box Protein P1 Is Dispensable for Retina but Essential for Lens Development.

Purpose: Forkhead box protein P1 (Foxp1) is a transcriptional repressor expressed in many tissues. We identified Foxp1 as a highly expressed gene in retinal progenitor cells and investigated its roles during eye development.

Methods: Mouse eyes with Foxp1 gain- or loss-of-function were established in vitro and in vivo.

Role of transcription factor Tgif2 in photoreceptor differentiation in the mouse retina.

5'TG3'-interacting factors (TGIFs) function as transcriptional repressors. Defects in TGIFs cause severe abnormalities in the developing brain and face. We found that Tgif2 was highly expressed in the mouse retina at early stages of development and examined its role in retinal development.

Conditional rod photoreceptor ablation reveals Sall1 as a microglial marker and regulator of microglial morphology in the retina.

Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte-derived macrophages into the CNS, resulting in the coexistence of these two populations within the same lesion, though their distinct features remain elusive. To investigate the impact of rod photoreceptor degeneration on microglial activation, we generated a toxin-mediated genetic model of rod degeneration. Rod injury induced microglial proliferation and migration toward the photoreceptors.

Identification of FoxR2 as an oncogene in medulloblastoma.

Medulloblastoma is the most common pediatric brain tumor, and in ∼25% of cases, it is driven by aberrant activation of the Sonic Hedgehog (SHH) pathway in granule neuron precursor (GNP) cells. In this study, we identified novel medulloblastoma driver genes through a transposon mutagenesis screen in the developing brain of wild-type and Trp53 mutant mice. Twenty-six candidates were identified along with established driver genes such as Gli1 and Crebbp.