Targets of FGFR2-IIIb signalling in the hair follicle
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE2463 | GEO | 2005/07/20
SECONDARY ACCESSION(S): PRJNA91169
REPOSITORIES: GEO
Similar Datasets
Project description:rationale: comparison of gene expression profiles in wildtype and Foxn1::dnFGFR2-IIIb transgenic hair follicles; identification of targets that mediate the effects seen in transgenic hair follicles; results: as already suggested by the phenotype, the molecular abnormalities appear to be restricted to the hair shaft medulla; Igfbp5 is an important mediator of transgene-dependent effects
2008-06-12 | E-GEOD-2463 | biostudies-arrayexpress
Project description:Hoxc13 has been shown to be essential for proper hair shaft differentiation as Hoxc13 gene-targeted (Hoxc13tm1Mrc) mice completely lack external hair. Because of the phenotypic parallels to the Foxn1nu (nude) mutant mice, we tested whether Hoxc13 and Foxn1 act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13tm1Mrc and Foxn1nu mice is due to strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These similarities are consistent with the overlap of Hoxc13 and Foxn1 expression patterns in the HF and nail matrix. DNA microarray analysis of scapular skin from Hoxc13tm1Mrc mutant (mut) compared to wild type (wt) mice identified Foxn1 as significantly down-regulated along with numerous hair keratin genes. This Foxn1 down-regulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-tranfection and chromatin immunoprecipitation (ChIP) assays. Total number of samples was 6. The experiment was perfomed in triplicate involving 3 indendent wild type skin samples (sample 1, 2, and 3) and 3 independent mutant skin samples (sample 4, 5, and 6).
2010-08-25 | E-GEOD-23759 | biostudies-arrayexpress
Project description:Hoxc13 has been shown to be essential for proper hair shaft differentiation as Hoxc13 gene-targeted (Hoxc13tm1Mrc) mice completely lack external hair. Because of the phenotypic parallels to the Foxn1nu (nude) mutant mice, we tested whether Hoxc13 and Foxn1 act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13tm1Mrc and Foxn1nu mice is due to strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These similarities are consistent with the overlap of Hoxc13 and Foxn1 expression patterns in the HF and nail matrix. DNA microarray analysis of scapular skin from Hoxc13tm1Mrc mutant (mut) compared to wild type (wt) mice identified Foxn1 as significantly down-regulated along with numerous hair keratin genes. This Foxn1 down-regulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-tranfection and chromatin immunoprecipitation (ChIP) assays.
2010-08-25 | GSE23759 | GEO
Project description:Mucopolysaccharidosis IIIB (MPS IIIB) is a rare genetic disorder caused by defects in α-N-acetylglucosaminidase, which breaks down extracellular heparan sulfate. Symptoms progress from hyperactivity and sleep disruptions during childhood to severe neurodegeneration during adolescence. To generate an MPS IIIB model in the fruitfly, Drosophila melanogaster, we introduced mutations in the corresponding fly enzyme that correlate with patient mutations. The fly model recapitulates sleep fragmentation and hyperactivity observed in patients and enlarged lysosomes in the brain. Genes associated with synaptic function and neurodevelopment showed altered expression in the brain. The Drosophila model can enable future development of therapies for MPS IIIB.
2025-03-26 | GSE269032 | GEO
Project description:Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of α-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegradedheparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. To identify potential biomarkers and novel neuropathological mechanisms of MPS IIIB, a label-free quantitative proteomic approach was applied to compare the proteome profile of brains from MPS IIIB and control mice. Proteins were identified through a bottom up analysis and 130 were significantly under-represented and 74 over-represented in MPS IIIB mouse brains compared to wild type (WT). Multiple bioinformatic analyses of the differentially abundant proteins allowed to define three major clusters: proteins involved in cytoskeletal regulation, synaptic vesicle trafficking, and energy metabolism. The results highlight the involvement of these clustered proteins in the neuropathology of MPS IIIB disease. The proteins identified in this study would provide potential targets for diagnostic and therapeutic studies of MPS IIIB.
2020-02-26 | PXD017363 | Pride
Project description:Background: Despite that vitamins or their derivatives (Vits), such as panthenyl ethyl ether, tocopherol acetate, or pyridoxine have been widely used in topical hair care products, their efficacy and mode of action have been insufficiently studied. Objective: To elucidate biological influence of Vits on hair follicles and dissect underlying mechanisms. Methods: Mouse vibrissa hair follicle organ culture model was utilized to evaluate the effects of Vits on hair shaft elongation. Gene and protein expression analyses, and histological investigation were conducted to elucidate responsible mechanisms. Human hair follicle cell culture was adopted to assess clinical relevance. Results: In organ culture models, the combination of panthenyl ethyl ether, tocopherol acetate, and pyridoxine (namely PPT) supplementation significantly promoted hair shaft elongation. PPT-treatment enhanced hair matrix cell proliferation by 1.9 folds compared to controls, as demonstrated by Ki-67 positive immunoreactivity. PPT-treated mouse dermal papillae up-regulated Placental growth factor (Plgf) by 1.6 folds, compared to non-treated controls. Importantly, addition of PlGF neutralizing antibodies to the ex vivo culture diminished the promotive effect on hair growth and the increase in VEGFR1 phosphorylation achieved by PPT. A VEGFR1 inhibitor also repressed the promotion of hair shaft elongation. Microarray analysis suggested synergistic summation of individual Vit bioactivity, putatively explaining the effect of PPT. Moreover, PPT increased PlGF secretion in cultured human dermal papilla cells. Conclusion: Our findings suggested that PPT promoted hair shaft elongation via activating PlGF/VEGFR-1 signaling. The current study can shed light on the previously underrepresented advantage of utilizing Vits for ameliorating hair care products.
2022-06-30 | GSE202865 | GEO
Project description:Since hair growth disorders can carry a major psychological burden, more effective human hair growth-modulatory agents need to be urgently developed. Here, we used the hypertrichosis-inducing immunosuppressant, cyclosporine A (CsA), as a lead compound to identify new hair growth-promoting targets. Through microarray analysis we identified the Wnt inhibitor, SFRP1, as being downregulated in the dermal papilla (DP) of CsA-treated human scalp hair follicles (HFs) ex vivo. Therefore, we further investigated the function of SFRP1 using a pharmacological approach and found that SFRP1 regulates intrafollicular canonical Wnt/β-catenin activity through inhibition of Wnt ligands in the human hair bulb. Conversely, inhibiting SFRP1 activity through the SFRP1 antagonist, WAY-316606, enhanced hair shaft production, hair shaft keratin expression and inhibited spontaneous HF regression (catagen) ex vivo. Collectively, these data (a) identify Wnt signaling as a novel, non-immune-inhibitory CsA target; (b) introduce SFRP1 as a physiologically important regulator of canonical β-catenin activity in a human (mini-)organ; and (c) demonstrate WAY-316606 to be a promising new promoter of human hair growth. Since inhibiting SFRP1 only facilitates Wnt signaling through ligands that are already present, this “ligand-limited” therapeutic strategy for promoting human hair growth may circumvent potential oncological risks associated with chronic Wnt over-activation. We used microarrays to identify novel hair growth promoting targets in human hair follicles through the use of cyclosporine A.
2018-05-09 | GSE109632 | GEO
Project description:EGFR targeted anti-cancer therapy induces severe skin toxicities, which affect life quality in patients. The lack of mechanistic details underlying these adverse events hampers their effective management. Here we identified EGFR as the epidermal master-regulator of the ERK pathway, which secures skin barrier integrity upon hair eruption. EGFR deficient epidermis displays a Th2-dominated expression signature and is permissive for excessive microbiota outgrowth. In the absence of EGFR, opening of the follicular ostia during hair eruption allows invasion of commensal microbiota aggravating barrier disruption and initiating an additional Th1 and Th17 response. Chronic folliculitis leads to Staphylococcus aureus dominated dysbiosis, further exacerbating inflammation and expanding barrier defects. Restoration of epidermal ERK signaling via therapeutic FGF7 treatment or transgenic SOS expression rescues skin barrier integrity in the absence of EGFR. These data reveal a gatekeeper function of the EGFR/ERK cascade in hair follicles securing the epidermal barrier around the erupting hair shaft.
2019-12-31 | GSE119376 | GEO
Project description:A Drosophila model of mucopolysaccharidosis IIIB
| PRJNA1119989 | ENA
Project description:Proteins of the human hair shaft contain a wealth of information about the coding regions of the person’s genome from whom the hair is derived. Commonly found at crime scenes, hair shafts may thus provide useful forensic evidence if the information they contain can be exploited. Present experiments show that hair shafts from four different anatomic sites are similarly useful in distinguishing individuals by protein profiling. However, the results demonstrated that protein profiles were dependent on anatomic site, indicating that a proper comparison requires matching the sites of origin. The differences in profile offer the prospect of determining the site of origin of hair by comparison with profiles of shafts from other anatomic sites. By contrast, the genetically variant peptides detected in the protein digests, that map to non-synonymous single nucleotide polymorphisms in subject DNA, were detectable regardless of the anatomic origin of the hair shafts. The resulting profiles of genetically variant peptides were more dependent on a subject’s genotype than on the anatomic origin of the hair shaft. Individual identification therefore can be based on peptide profiles regardless of body location. This study demonstrates the utility of proteomic analysis for increasing the forensic value of hair shaft evidence.
2019-04-04 | PXD011732 | Pride