The Mitf-Tfe family of basic helix–loop–helix-leucine zipper (bHLH-Zip) transcription factors encodes four members: Mitf, Tfe3, Tfeb, and Tfec. In vitro , each protein in the can bind DNA as a homo- or heterodimer with other members. Mutational studies mice have shown that Mitf is essential for melanocyte eye development, whereas Tfeb required placental vascularization. Here, we uncover role Tfe3 osteoclast functionally redundant . Although osteoclasts seem normal null mice, combined loss...

ABSTRACT Genetic and cell culture analyses have shown that the development of melanocytes from neural crest-derived precursor cells critically depends on tyrosine kinase receptor KIT basic-helix-loop-helix-leucine zipper transcription factor MITF. MITF show complex interactions in is needed for maintenance Kit expression melanoblasts signaling modulates activity stability melanocyte lines. Using primary crest cultures embryos homozygous a null allele marked by an inserted LacZ gene...

There is increasing indication that interspecific phenotypic differences result from variations in gene-regulatory interactions. Here we provide evidence mice differ zebrafish the way they use homologous key components to regulate pigment cell differentiation. In both and mice, one transcription factor, SOX10, controls expression of another, MITF (microphthalmia-associated factor), which turn regulates a set genes critical for development pigmentation. Mutations either Sox10 or Mitf impair...

ADAMTS20 (A disintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of family secreted metalloproteases that can process variety extracellular matrix (ECM) components molecules. Adamts20 mutations in belted (bt) mice cause white spotting the dorsal ventral torso, indicative defective neural crest (NC)-derived melanoblast development. The expression pattern dermal mesenchymal cells adjacent to migrating melanoblasts led us initially propose regulated...

Retinal pigment epithelial (RPE) cells play important roles in ophthalmologic diseases such as proliferative vitreoretinopathy, AMD, and diabetic retinopathy. MicroRNA-34a (miR-34a) has been reported to be the regulation of cell proliferation, migration, differentiation, apoptosis. In this study, we explored effects miR-34a on RPE cells.The expression level subconfluent postconfluent ARPE-19 was investigated with quantitative real-time PCR. MicroRNA mimic small interfering RNA (siRNA) were...

Summary There is growing evidence that micro RNA s are important regulators of gene expression in a variety cell types. Using immortalized lines and primary neural crest explants, we show ‐211, previously implicated the regulation melanoma proliferation invasiveness, promotes pigmentation melanoblasts melanocytes. Expression this regulated by key melanocyte transcription factor MITF regulates targeting TGF ‐ β receptor 2. Transfection with pre‐miR‐211 precursor molecules melb‐a melan‐a cells...

Pmel 17 is preferentially expressed in pigment cells a manner suggestive of involvement melanin biosynthesis. The gene identical to the silver (si) pigmentation locus mice. We now produced recombinant glutathione-S-transferase-human infusion protein and raised polyclonal antibodies against it confirm ultrastructural location presumed site action predicted by deduced primary structure 17/silver, authenticate specificity DHICA converting function as inherent silver-locus protein. Full-length...

In response to various types of injury, melanocyte stem cells (McSCs) located in the bulge hair follicles can regenerate mature melanocytes for and skin pigmentation. How McSCs respond however, remains largely unknown. Here we show that after epilation mice, follicular epidermal melanocytes, resulting hyperpigmentation. We further leads endogenous EDN3 upregulation dermal papilla, secondary germ cells, epidermis. Genetic pharmacological disruption receptor EDNRB vivo significantly blocks...

Oxidative damage is one of the major contributors to retinal degenerative diseases such as age-related macular degeneration (AMD), while RPE mediated antioxidant defense plays an important role in preventing retinopathies. However, regulatory mechanisms signaling cells are poorly understood. Here we show that transcription factor MITF regulates response cells, protecting neural retina from oxidative damage. In stress-induced mouse model, Mitf+/- mice significantly aggravated compared WT...

Abstract Background Oxidative stress is a common cause of neurodegeneration and plays central role in retinal degenerative diseases. Heme oxygenase-1 (HMOX1) redox-regulated enzyme that induced neurodegenerative diseases acts against oxidative but can also promote cell death, phenomenon still unexplained molecular terms. Here, we test whether HMOX1 has opposing effects during degeneration investigate the mechanisms behind its pro-apoptotic role. Methods Basal levels retinas are examined...

To study the clinical manifestations and genetic characteristics of children with maturity-onset diabetes young type 2 (MODY2), aiming to enhance recognition MODY2 in practice. A retrospective analysis was conducted on data 13 diagnosed at Department Pediatrics Tongji Hospital Medical College Huazhong University Science Technology from August 2017 July 2023. All had a positive family history were found have mild fasting hyperglycemia [(6.4±0.5) mmol/L] during health examinations or due...

Abstract Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) proliferative vitreoretinopathy (PVR). Although absent melanoma 2 (AIM2) has been linked inflammatory disorders, autoimmune cancers, its role the EMT of pigment epithelium (RPE-EMT) diseases remains unclear. The present study demonstrated...

To better understand the distinct functional roles of 220- and 130-kDa forms myosin light chain kinase (MLCK), expression intracellular localization were determined during development in adult mouse tissues. Northern blot, Western histochemical studies show that 220-kDa MLCK is widely expressed as well several smooth muscle nonmuscle The highly all tissues examined also detectable embryonic development. Colocalization examining distribution 130- MLCKs revealed colocalizes with IIA but not...

The endothelin receptor B gene (Ednrb) encodes a G-protein-coupled that is expressed in variety of cell types and specifically required for the development neural crest-derived melanocytes enteric ganglia. In humans, mutations this are associated with Waardenburg-Shah syndrome, disorder characterized by pigmentation defects, deafness megacolon. To address question whether melanocyte depends entirely on cell-autonomous action Ednrb, we performed series tissue recombination experiments vitro,...

Haploinsufficiency for the transcription factor SOX10 is associated with pigmentary deficiencies of Waardenburg syndrome (WS) and modeled in Sox10 haploinsufficient mice (Sox10LacZ/+). As genetic background affects WS severity both humans mice, we established an N-ethyl-N-nitrosourea (ENU) mutagenesis screen to identify modifiers that increase phenotypic Sox10LacZ/+ mice. Analysis 230 pedigrees identified three modifiers, named modifier neurocristopathies (Mos1, Mos2 Mos3). Linkage analysis...

This study aimed to investigate the cancer stem cell (CSC) properties of radioresistant esophageal cells and radiosensitization effect NS398, a cyclooxygenase (COX)-2 inhibitor, on them. Fractionated irradiation was applied acquire cells. Clone formation assay employed detect radiosensitivity cloning ability. Cell viability determined by methyl tetrazolium colorimetry assay. cycle distribution apoptosis were detected flow cytometry. Tumorigenicity investigated xenograft tumorigenicity...

Abstract Regeneration of the visual pigment by cells retinal epithelium (RPE) is fundamental to vision. Here we show that microphthalmia-associated transcription factor, MITF, which plays a central role in development and function RPE cells, regulates expression two cycle genes, Rlbp1 encodes retinaldehyde binding protein-1 (RLBP1) Rdh5 , retinol dehydrogenase-5 (RDH5). First, found are downregulated optic cups presumptive RPEs Mitf -deficient mouse embryos. Second, experimental manipulation...

ABSTRACT Dysfunction and loss of the retinal pigment epithelium (RPE) are hallmarks degeneration, but underlying pathogenetic processes only partially understood. Using mice with a null mutation in transcription factor gene Mitf, which RPE deficiencies associated we evaluated role trophic factors secreted by homeostasis. In such mice, thickness outer nuclear layer (ONL) is as wild type up to postnatal day 10, then progressively reduced, marked increase number apoptotic cells decline staining...

In this study, two alternatively spliced forms of the mouse death-associated protein kinase (DAPK) have been identified and their roles in apoptosis examined. The DAPK-α sequence is 95% identical to previously described human DAPK, it has a domain calmodulin-binding region closely related 130–150 kDa myosin light chain kinases. A 12-residue extension carboxyl terminus DAPK-β distinguishes from DAPK-α. DAPK phosphorylates at least one substrate <i>in vitro</i> vivo</i>, II regulatory chain....