Background Tubulin is a major substrate of the cytoplasmic class II histone deacetylase HDAC6. Inhibition HDAC6 results in higher levels acetylated tubulin and enhanced binding motor protein kinesin-1 to tubulin, which promotes transport cargoes along microtubules. Microtubule-dependent intracellular trafficking may therefore be regulated by modulating activity We have shown previously that neuromodulator serotonin increases mitochondrial movement hippocampal neurons via Akt-GSK3β signaling...

ABSTRACT We investigated the mechanism of tissue induction and specification using lacrimal gland as a model system. This structure begins its morphogenesis bud-like outgrowth conjunctival epithelium ultimately forms branched with secretory function. Using reporter transgene specific marker for epithelium, we show that transcription factor Pax6 is required normal development probably an important competence factor. In investigating cell-cell signaling required, fibroblast growth (FGF) 10...

Manipulation of the interaction a morphogen with extracellular matrix changes its biological activities by altering diffusion.

We describe experiments showing that fibroblast growth factor receptor (Fgfr) signaling plays a role in lens induction. Three distinct experimental strategies were used: (1) using small-molecule inhibitors of Fgfr kinase activity, we showed both the transcription level and protein expression Pax6, critical for development, was diminished presumptive ectoderm; (2) transgenic mice (designated Tfr7) expressed dominant-negative Fgf exclusively ectoderm defects formation placode at E9.5 but...

We have investigated the role of Bmp signaling in development mouse lens using three experimental strategies. First, we shown that ligand inhibitor noggin can suppress differentiation primary fiber cells explant culture. Second, expressed a dominant-negative form type 1 family receptor Alk6 (Bmpr1b – Mouse Genome Informatics) transgenic mice and an inhibition cell be detected at E13.5. Interestingly, observed was asymmetrical appeared only on nasal side ventral half. Expression inhibitory...

Recent studies have shown that various neural and embryonic stem cells cultured in 1-8% oxygen (O(2)), levels lower than those typically used cell culture (20.9%), displayed increased rates of proliferation; however, the molecular mechanisms underlying these changes are largely undefined. In this study, using rigorously controlled O(2) levels, we found (NSCs) from day 15 rat cortex their rate proliferation migration 1% relative to 20% without viability. We sought identify NSCs grown might...

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived and critical regulator of fetal organ development in mice humans. Using single-cell RNA sequencing (RNA-seq) atlas salivary gland (SG) tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there switch expression only epithelial observed P15. Further RNA-seq analysis sorted shows the population express hallmarks...

Embryonic submandibular salivary gland (SMG) initiation and branching morphogenesis are dependent on cell-cell communications between within epithelium mesenchyme. Such typically mediated in other organs (teeth, lung, lacrimal glands) by growth factors such a way as to translate autocrine, juxtacrine paracrine signals into specific gene responses regulating cell division histodifferentiation. Using Wnt1-Cre/R26R transgenic mice, we demonstrate that embryonic SMG mesenchyme is derived...

The Pax6 gene has a central role in development of the eye. We show, through targeted deletion mouse, that an ectoderm enhancer is required for normal lens formation. Ectoderm enhancer-deficient embryos exhibit distinctive defects at every stage development. These include thinner placode, reduced placodal cell proliferation, and small pit vesicle. In addition, vesicle fails to separate from surface maturing smaller shows delay fiber differentiation. Interestingly, does not eliminate...

The lacrimal gland (LG) develops through branching morphogenesis and produces secretions, including tears, that lubricate protect the ocular surface. Despite prevalence of LG disorders such as dry eye, relatively little is known about regulation development. In this study, we show homeobox transcription factor Barx2 highly expressed in conjunctival epithelium, eyelids [lacrimal, harderian (HG), meibomian (MG)] glands necessary for normal eyelid Barx2–/– mice defective morphogenesis, absence...

It is important to understand how muscle forms normally in order diseases that result abnormal formation. Although the structure of myofibrils well understood, process through which myofibril components form organized contractile units not clear. Based on staining proteins avian embryonic cardiomyocytes, we previously proposed formation occurred steps began with premyofibrils followed by nascent and ending mature myofibrils. The purpose this study was determine whether premyofibril model...

Abstract In humans, the lacrimal gland (LG) is primary contributor to aqueous layer of tear film. Production tears in insufficient quantity or inadequate quality may lead aqueous-deficiency dry eye (ADDE). Currently there no cure for ADDE. The development strategies reliably isolate LG stem/progenitor cells from tissue brings great promise design cell replacement therapies patients with We analyzed therapeutic potential epithelial progenitor (EPCPs) isolated adult wild-type mouse LGs by...

To identify changes in the expression of genes coding for extracellular matrix (ECM) proteins patients with non-inflammatory corneal disorder keratoconus (KC), scarring, and normal controls.Total RNA extracted from tissue 13 KC patients, 2 scaring 4 controls was analyzed using Human Extracellular Matrix & Adhesion Molecules Profiler PCR Array. Statistically significant gene were identified Data Analysis software.Comparison control corneas thresholds 1.5 or greater fold change a p-value 0.05...

Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates suggest ectopic structures. However, these structures have not been fully investigated. Using mice of different ages, we analyzed the transcriptome murine LGs and characterized B T cell populations. Age-related changes LG include differentially expressed genes associated with activation, germinal center...

Among the many factors involved in regulation of chondrogenesis, bone morphogenetic proteins (BMPs) and members Sox homeobox transcription factor families have been shown to crucial roles. Of these regulators, that function during chondrogenesis least well defined. We show here Barx2 is expressed primary mesenchymal condensations, digital rays, developing joints articular cartilage limb, suggesting it plays a role chondrogenesis. Using retroviruses antisense oligonucleotides manipulate...

The lacrimal gland provides an excellent model with which to study the epithelial-mesenchymal interactions that are crucial process of branching morphogenesis. In current study, we show bone morphogenetic protein 7 (Bmp7) is expressed a complex pattern in developing and has important role regulating branching. loss-of-function analyses, find Bmp7-null mice have distinctive reductions branch number, inhibition Bmp activity explant cultures very similar consequence. Consistent this,exposure...

Abstract Regeneration is a process that restores structure and function of tissues damaged by injury or disease. In mammals complete regeneration often unsuccessful, while most the low phyla animals can re-grow many parts their body after amputation. Cephalopod molluscs, in particular Octopus vulgaris , are well known for capacity to regenerate arms other parts, including central peripheral nervous system. To better understand mechanism recovery following nerve this species we investigated...

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed pathway during acute and chronic investigated its potential regulators. Bacterial infection was mimicked intraglandular injection of lipopolysaccharide (LPS) nigericin, known to activate NLRP3 inflammasome. Acute injury lacrimal induced interleukin (IL)-1α injection. Chronic studied...