TOB1 and TOB2 mark distinct RNA processing granules in differentiating lens fiber cells.

Differentiation of lens fiber cells involves a complex interplay of signals from growth factors together with tightly regulated gene expression via transcriptional and post-transcriptional regulators. Various studies have demonstrated that RNA-binding proteins, functioning in ribonucleoprotein granules, have important roles in regulating post-transcriptional expression during lens development. In this study, we examined the expression and localization of two members of the BTG/TOB family of RNA-binding proteins, TOB1 and TOB2, in the developing lens and examined the phenotype of mice that lack Tob1.

Genotype, Age, Genetic Background, and Sex Influence Epha2-Related Cataract Development in Mice.

Purpose: Age-related cataract is the leading cause of blindness worldwide. Variants in the EPHA2 gene increase the disease risk, and its knockout in mice causes cataract. We investigated whether age, sex, and genetic background, risk factors for age-related cataract, and Epha2 genotype influence Epha2-related cataract development in mice.

Neural differentiation medium for human pluripotent stem cells to model physiological glucose levels in human brain.

Cortical neurospheres (NSPs) derived from human pluripotent stem cells (hPSC), have proven to be a successful platform to investigate human brain development and neuro-related diseases. Currently, many of the standard hPSC neural differentiation media, use concentrations of glucose (approximately 17.5-25 mM) and insulin (approximately 3.

Photoreceptor Degeneration in Pro23His Transgenic Rats (Line 3) Involves Autophagic and Necroptotic Mechanisms.

Photoreceptor death contributes to 50% of irreversible vision loss in the western world. Pro23His (P23H) transgenic albino rat strains are widely used models for the most common rhodopsin gene mutation associated with the autosomal dominant form of retinitis pigmentosa. However, the mechanism(s) by which photoreceptor death occurs are not well understood and were the principal aim of this study.

Ocular Phenotype of Relaxin Gene Knockout (Rln) Mice.

: To test if relaxin deficiency affects ocular structure and function we investigated expression of relaxin () and RXFP receptors (), and compared ocular phenotypes in relaxin gene knockout ( ) and wild type ( ) mice. : and mRNA expression was detected in ocular tissues of Rln+/+ mice using RT-PCR. The eyes of 11 and 5 male mice were investigated.

Epha2 genotype influences ultraviolet radiation induced cataract in mice.

Age-related cataract is the major cause of blindness worldwide. Both genetic and environmental factors contribute to the disease. Genetic variation in the Ephrin type-A receptor 2 (EPHA2) gene is associated with the risk of age-related cataract in multiple populations, and exposure to ultraviolet-B (UV-B) radiation is a well-established risk factor for the disease.

Exposure of trophoblast cells to fine particulate matter air pollution leads to growth inhibition, inflammation and ER stress.

Ambient air pollution is considered a major environmental health threat to pregnant women. Our previous work has shown an association between exposure to airborne particulate matter (PM) and an increased risk of developing pre-eclamspia. It is now recognized that many pregnancy complications are due to underlying placental dysfunction, and this tissue plays a pivotal role in pre-eclamspia.

Altered airway ciliary orientation in patients with X-linked retinitis pigmentosa.

Previous reports suggested links between respiratory ciliary dysfunction and primary ciliopathies such as X-linked retinitis pigmentosa (XLRP). To investigate if patients with XLRP have abnormal airway ciliary structure or function, we assessed respiratory ciliary beat pattern and ultrastructure, including ciliary orientation, in 12 patients with XLRP without respiratory disease and 10 control subjects. Patients with XLRP had normal ciliary ultrastructure but significantly (p=0.

Esrp1 is a marker of mouse fetal germ cells and differentially expressed during spermatogenesis.

ESRP1 regulates alternative splicing, producing multiple transcripts from its target genes in epithelial tissues. It is upregulated during mesenchymal to epithelial transition associated with reprogramming of fibroblasts to iPS cells and has been linked to pluripotency. Mouse fetal germ cells are the founders of the adult gonadal lineages and we found that Esrp1 mRNA was expressed in both male and female germ cells but not in gonadal somatic cells at various stages of gonadal development (E12.

Altered SOX9 genital tubercle enhancer region in hypospadias.

Human mutations in the SOX9 gene or its regulatory region can disrupt testicular development, leading to disorders of sex development (DSDs). Our previous work involving the genomic analysis of isolated DSD patients revealed a 78kb minimal sex determining region (RevSex) far upstream of SOX9 that was duplicated in 46,XX and deleted in 46,XY DSDs. It was postulated that RevSex contains a gonadal enhancer.

Localization and Possible Function of P2X Receptors in Normal and Diseased Retinae.

Purines, when present in the extracellular space, can mediate fast neurotransmission in the retina and central nervous system. Over the last decade there has been emerging evidence for the expression of P2X and P2Y receptors in a range of retinal neuronal subtypes. These results have highlighted important roles for purines in modulating specific retinal circuits, including the rod pathway and amacrine cell circuits.

Tob1 is expressed in developing and adult gonads and is associated with the P-body marker, Dcp2.

Tob1 is a member of the BTG/TOB family of proteins with established antiproliferative function. In Danio rerio and Xenopus laevis, the Tob1 gene is expressed from the one-cell stage through to early gastrula stages, followed in later development by discrete expression in many tissues including the notochord and somites. In both mouse and human, Tob1 is expressed in many adult tissues including the testis and ovary; however, the specific cell types are unknown.

Expression analysis of Cdx2 and Pou5f1 in a marsupial, the stripe-faced dunnart, during early development.

The first lineage allocation during mouse development forms the trophectoderm and inner cell mass, in which Cdx2 and Pou5f1 display reciprocal expression. Yet Cdx2 is not required for trophectoderm specification in other mammals, such as the human, cow, pig, or in two marsupials, the tammar and opossum. The role of Cdx2 and Pou5f1 in the first lineage allocation of Sminthopsis macroura, the stripe-faced dunnart, is unknown.

Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration.

While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei.

A role for smoothened during murine lens and cornea development.

Various studies suggest that Hedgehog (Hh) signalling plays roles in human and zebrafish ocular development. Recent studies (Kerr et al., Invest Ophthalmol Vis Sci.

Studying age-related macular degeneration using animal models.

Over the recent years, there have been tremendous advances in our understanding of the genetic and environmental factors associated with the development of age-related macular degeneration (AMD). Examination of retinal changes in various animals has aided our understanding of the pathogenesis of the disease. Notably, mouse strains, carrying genetic anomalies similar to those affecting humans, have provided a foundation for understanding how various genetic risk factors affect retinal integrity.

Integrin linked kinase (ILK) is required for lens epithelial cell survival, proliferation and differentiation.

While the role of growth factors in lens development has been investigated extensively, the role of extracellular matrix signalling is less well understood. The developing lens expresses predominantly laminin-binding integrins (such as α3β1, α6β1), which are cooperatively required in the lens epithelium during development. We investigated the role of ILK, a downstream mediator of integrin signalling in mice conditionally null for Ilk.

A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture.

Background: Embryonic stem (ES) cells hold considerable promise as a source of cells with therapeutic potential, including cells that can be used for drug screening and in cell replacement therapies. Differentiation of ES cells into the somatic lineages is a regulated process; before the promise of these cells can be realised robust and rational methods for directing differentiation into normal, functional and safe cells need to be developed. Previous in vivo studies have implicated fibroblast growth factor (FGF) signalling in lineage specification from pluripotent cells.

Conditional mutations of beta-catenin and APC reveal roles for canonical Wnt signaling in lens differentiation.

Purpose: Previous studies indicate that the Wnt/beta-catenin-signaling pathway is active and functional during murine lens development. In this study, the consequences of constitutively activating the pathway in lens during development were investigated.

Methods: To activate Wnt/beta-catenin signaling, beta-catenin (Catnb) and adenomatous polyposis coli (Apc) genes were conditionally mutated in two Cre lines that are active in whole lens (MLR10) or only in differentiated fibers (MLR39), from E13.

Differential requirement for beta-catenin in epithelial and fiber cells during lens development.

Recent studies implicate Wnt/beta-catenin signaling in lens differentiation (Stump, R. J., et al.

Extracellular matrix and integrin signaling in lens development and cataract.

During development of the vertebrate lens there are dynamic interactions between the extracellular matrix (ECM) of the lens capsule and lens cells. Disruption of the ECM causes perturbation of lens development and cataract. Similarly, changes in cell signaling can result in abnormal ECM and cataract.