Pax6

Vestigial organs provide a link between ancient and modern traits and therefore have great potential to resolve the phylogeny of contentious fossils that bear features not seen in extant species. Here we show that extant daddy-longlegs (Arachnida, Opiliones), a group once thought to possess only one pair of eyes, in fact additionally retain a pair of vestigial median eyes and a pair of vestigial lateral eyes. Neuroanatomical gene expression surveys of eye-patterning transcription factors, opsins, and other structural proteins in the daddy-longlegs Phalangium opilio show that the vestigial median and lateral eyes innervate regions of the brain positionally homologous to the median and lateral eye neuropils, respectively, of chelicerate groups like spiders and horseshoe crabs...

Limbal niche cells (LNCs) are one of the most important supporting cells for corneal epithelial stem cells (CES), however, research on LNCs has been mostly limited to humans and rats previously. To expand the research work into the rabbit animal model, one of the most often used animals in stem cell study, this study was carried out for the in vitro isolation and identification of rabbit LNCs. Rabbit LNCs were isolated by collagenase A digestion method and single cells were obtained, the cells were then seeded on 5% Matrigel-coated plastic surface and cultured in modified embryonic stem cell medium (MESCM)...

Enrichment of basal progenitors (BPs) in the developing neocortex is a central driver of cortical enlargement. The transcription factor Pax6 is known as an essential regulator in generation of BPs. H3 lysine 9 acetylation (H3K9ac) has emerged as a crucial epigenetic mechanism that activates the gene expression program required for BP pool amplification. In this current work, we applied immunohistochemistry, RNA sequencing, chromatin immunoprecipitation and sequencing, and the yeast two-hybrid assay to reveal that the BP-genic effect of H3 acetylation is dependent on Pax6 functionality in the developing mouse cortex...

Internal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were used to administer VPA (200 μg/g body weight) on postnatal days 6 and 7. EdU and BrdU were injected on postnatal days 5 and 7, respectively, to label the post-proliferative and proliferating cells when exposed to VPA...

OBJECTIVE: To investigate the correlation of maternal PDX1 methylation, NGN3 and Pax6 expression levels with neonatal blood sugars and birth weight in pregnant women with GDM and non GDM. METHODS: This was a prospective cohort study. Total 80 pregnant women who were examined and delivered in the Department of Obstetrics of Affiliated Hospital of Hebei University from January 2019 to June 2022 were recruited and divided into two groups according to the results of oral glucose tolerance test (OGTT): the control group and the observation group, with 40 cases in each group...

Pulpitis is a common dental emergency that presents with intense pain; there is still no specific medicine to treat pulpitis-induced pain to date. Herein, differentially expressed genes in mouse anterior cingulate cortex (ACC) were investigated 7 days after pulp exposure via a combination of high-throughput transcriptomic and proteomic analyses. We screened 34 key genes associated with 8 critical pathways. Among these, genes (Elovl5, Ikbke, and Nbeal2) involved in immune or inflammatory responses exhibited exclusive regulation at the transcriptomic level, as confirmed by qRT-PCR...

AIMS: Numerous studies on animals have shown that exposure to general anesthetics in infant stage may cause neurocognitive impairment. However, the exact mechanism is not clear. The dysfunction of iron metabolism can cause neurodevelopmental disorders. Therefore, we investigated the effect of iron metabolism disorder induced by sevoflurane (Sev) on cognitive function and the proliferation of neural precursor cells (NPCs) and neural stem cells (NSCs) in infant mice. METHODS: C57BL/6 mice of postnatal day 14 and neural stem cells NE4C were treated with 2% Sev for 6 h...

Optic neuropathies, such as glaucoma, are due to progressive retinal ganglion cells (RGCs) degeneration, result in irreversible vision loss. The promising RGCs replacement therapy for restoring vision are impeded by insufficient RGC-like cells sources. The present work was enriched one new type RGC-like cells using two surface markers CD184 and CD171 from human induced pluripotent stem cells (hiPSCs) by FACS sorting firstly. These new kind cells have well proliferation ability and possessed passage tolerance in vitro 2D or 3D spheroids culture, which kept expressing Pax6, Brn3b and βIII-Tubulin and so on...

Colorectal cancer is a cancer that arises from the abnormal growth of cells in the colon or rectum. Osteosarcoma (OS) is a common primary bone tumor with high degree of malignancy. The configuration files for colorectal cancer dataset GSE142279 and OS datasets GSE197158 and GSE206448 were downloaded from Gene Expression Omnibus database using the platforms GPL20795, GPL20301, and GPL24676. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed...

This study investigates a unique and complex eye phenotype characterized by minimal iris defects, foveal hypoplasia, optic nerve coloboma, and severe posterior segment damage. Through genetic analysis and bioinformatic tools, a specific nonsynonymous substitution, p.(Asn114Ser), within the PAX6 gene's paired domain is identified. Although this substitution is not in direct contact with DNA, its predicted stabilizing effect on the protein structure challenges the traditional understanding of PAX6 mutations, suggesting a gain-of-function mechanism...

BACKGROUNDS: Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort. METHODS: A total of 75 probands with simplex uHM were included in our Pediatric and Genetic Eye Clinic. Patients with significant posterior anomalies other than myopic fundus changes were excluded...

BACKGROUND: This study aims to characterize optic disc hypoplasia in congenital aniridia using ultra-wide-field imaging (UWFI) and nonmydriatic retinal photography (NMRP). We also investigated the relation between optic disc hypoplasia and foveal hypoplasia. METHODS: This is a retrospective case series of patients diagnosed with PAX6-related aniridia in a National Referral Center, who underwent UWFI, NMRP, and spectral-domain optical coherence tomography (SD-OCT)...

BACKGROUND: Deletion of haploinsufficient genes or duplication of triplosensitive ones results in phenotypic effects in a concentration-dependent manner, and the mechanisms underlying these dosage-sensitive effects remain elusive. Phase separation drives functional compartmentalization of biomolecules in a concentration-dependent manner as well, which suggests a potential link between these two processes, and warrants further systematic investigation. RESULTS: Here we provide bioinformatic and experimental evidence to show a close link between phase separation and dosage sensitivity...

UNLABELLED: Meningioma is a common brain tumour which has neither a specific detection nor treatment method. The Sonic hedgehog (Shh) cell signaling pathway is a crucial regulatory pathway of mammalian organogenesis and tumorigenesis including meningioma. Shh cell signalling pathway cascade function by main transcription factor Gli1 and which further regulates in its downstream to Pax6 and Nkx2.2. This current study is aimed to explore the regulation of the Sonic hedgehog-Gli1 cell signaling pathway and its potential downstream targets in meningioma samples...

The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13 exposure increases goblet and tuft cell differentiation and drastically modifies the conjunctiva secretome...

Up to 50% of patients with severe congenital heart disease (CHD) develop life-altering neurodevelopmental disability (NDD). It has been presumed that NDD arises in CHD cases because of hypoxia before, during, or after cardiac surgery. Recent studies detected an enrichment in de novo mutations in CHD and NDD, as well as significant overlap between CHD and NDD candidate genes. However, there is limited evidence demonstrating that genes causing CHD can produce NDD independent of hypoxia. A patient with hypoplastic left heart syndrome and gross motor delay presented with a de novo mutation in SMC5 ...

BACKGROUND: 5' untranslated regions (5'UTRs) are essential modulators of protein translation. Predicting the impact of 5'UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5'UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs). METHODS: We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina...

Human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) therapies are promising alternatives for the treatment of retinal degenerative diseases caused by RPE degeneration. The generation of autologous RPE cells from human adult donors, which has the advantage of avoiding immune rejection and teratoma formation, is an alternative cell resource to gain mechanistic insight into and test potential therapies for RPE degenerative diseases. Here, we found that limbal stem cells (LSCs) from hESCs and adult primary human limbus have the potential to produce RPE cells and corneal stromal stem cells (CSSCs)...

Rett Syndrome (RTT) is a severe neurodevelopmental disorder, afflicting 1 in 10,000 female births. It is caused by mutations in the X-linked MECP2 gene, which encodes for the global transcriptional regulator MeCP2. As human brain samples of RTT patients are scarce and cannot be used for downstream studies, there is a pressing need for in vitro modeling of pathological neuronal changes. Here, we employ a direct reprogramming method for the generation of neuronal cells from MeCP2-deficient and wildtype human dermal fibroblasts using two episomal plasmids encoding the transcription factors SOX2 and PAX6...

Although ionizing radiation (IR) is widely used for therapeutic and research purposes, studies on low-dose ionizing radiation (LDIR) are limited compared with those on other IR approaches, such as high-dose gamma irradiation and ultraviolet irradiation. High-dose IR affects DNA damage response and nucleotide-protein crosslinking, among other processes; however, the molecular consequences of LDIR have been poorly investigated. Here, we developed a method to profile RNA species crosslinked to an RNA-binding protein, namely, human antigen R (HuR), using LDIR and high-throughput RNA sequencing...