The Experts below are selected from a list of 4422 Experts worldwide ranked by ideXlab platform
David Schlessinger - One of the best experts on this subject based on the ideXlab platform.
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eda activated relb recruits an swi snf baf chromatin remodeling complex and initiates gene transcription in Skin Appendage formation
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David SchlessingerAbstract:Ectodysplasin A (Eda) signaling activates NF-κB during Skin Appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in Skin Appendages, and epidermal knockout of BAF250a impairs Skin Appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
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Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in Skin Appendage formation.
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David SchlessingerAbstract:Ectodysplasin A (Eda) signaling activates NF-κB during Skin Appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in Skin Appendages, and epidermal knockout of BAF250a impairs Skin Appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
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EDA signaling and Skin Appendage development.
Cell cycle (Georgetown Tex.), 2006Co-Authors: Chang-yi Cui, David SchlessingerAbstract:The same morphogenetic signals are often involved in the development of different organs. For developing Skin Appendages, a model for tissue-specific regulation of signaling is provided by the EDA pathway, which accesses the otherwise ubiquitous NFkappaB transcription factors. EDA signaling is mediated by ectodysplasin, EDAR and EDARADD, which form a new TNF ligand-receptor-adaptor family that is restricted to Skin Appendages in vertebrates from fish to human. The critical function of the pathway was demonstrated in the hereditary genetic disorder Anhidrotic Ectodermal Dysplasia (EDA), which is characterized by defective formation of hair follicles, sweat glands and teeth. The pathway does not appear to initiate the development of the Appendages, but is regulated by and regulates the course of further morphogenesis. In mice, transgenic and knockout strains have increasingly revealed features of the mechanism, and suggest possible non-invasive interventions to alleviate EDA deficiency, especially in sweat glands and eyes.
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inducible meda a1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles
Human Molecular Genetics, 2003Co-Authors: Meredith C Durmowicz, Chris Ottolenghi, Tsuyoshi Hashimoto, Bradley L Griggs, Anand K Srivastava, David SchlessingerAbstract:EDA splice isoforms EDA-A1 and EDA-A2 belong to the TNF ligand family and regulate Skin Appendage formation by activating NF-kB- and JNK- promoted transcription. To analyze their action further, we conditionally expressed the isoforms as tetracycline (‘Tet’)-regulated transgenes in Tabby (EDA-negative) and wild-type mice. Expression of only the mEDA-A1 transgene had two types of effects during embryogenesis: (1) determinative effects on sweat glands and hair follicles. In Tabby mice, one type of hair follicle (‘guard hair’) was restored, whereas a second type, the dominant undercoat hair follicle (‘zigzag’) was not; furthermore, the transgene sharply suppressed zigzag hair formation in wild-type mice, with the overall numbers of back hair follicles remaining the same; and (2) trophic effects on sebaceous and Meibomian glands. Marked hyperplasia resulted from expansion of the sebocyte-producing zone in sebaceous glands, with particularly high expression of the transgene and the replication marker PCNA, and correspondingly high production of sebum. The phenotypic effects of mEDA-A1 on sebaceous glands, but not on hair follicles, were reversed when the gene was repressed in adult animals. The results thus reveal both initiating and trophic isoform-specific effects of the EDA gene, and suggest a possible balance of isoform interactions in Skin Appendage formation.
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eda targets revealed by Skin gene expression profiles of wild type tabby and tabby eda a1 transgenic mice
Human Molecular Genetics, 2002Co-Authors: Chang-yi Cui, Ken Hashimoto, Meredith C Durmowicz, Anand K Srivastava, David Schlessinger, Tetsuya S Tanaka, Andrew J Hartung, Tadashi TezukaAbstract:Mutations in the EDA gene cause anhidrotic ectodermal dysplasia (EDA), with lesions in Skin Appendage formation. To begin to analyze EDA pathways, we have used expression profiling on 15,000-gene mouse cDNA microarrays, comparing adult mouse Skin from wild-type, EDA-defective (Tabby) mice, and Tabby mice supplemented with the EDA-A1 isoform, which is sufficient to rescue multiple Tabby phenotypes. Given the sensitivity of the current microarray system, 8500 genes (60%) were estimated to be expressed, including transcription factors and growth-regulatory genes that had not previously been identified in Skin; but only 24 (0.16%), one-third of them novel, showed significant differences between wild type and Tabby. An additional eight genes not included in the 15,000 gene set were shown to have expression differences by real-time RT-PCR. Sixteen of 32 affected genes were restored significantly toward wild-type levels in EDA-A1 transgenic Tabby mice. Significant up-regulation in Tabby Skin was observed for several dermal matrix genes, including Col1a1, Col1a2, Col3a1 and SPARC: In contrast, down-regulation occurred for the NEMO/NF-kappa B pathway, already implicated in Skin Appendage formation, and even more markedly for a second pathway, JNK/c-jun/c-fos and their target genes, that has not previously been clearly associated with Skin development. These data are consistent with the regulation of the NF-kappa B pathway by EDA, and support its involvement in the regulation of the JNK pathway as well.
Marja L Mikkola - One of the best experts on this subject based on the ideXlab platform.
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expression of foxi3 is regulated by ectodysplasin in Skin Appendage placodes
Developmental Dynamics, 2013Co-Authors: Vera Shirokova, Maria Jussila, Marjo K Hytonen, Nina Perala, Cord Drogemuller, Tosso Leeb, Hannes Lohi, Kirsi Sainio, Irma Thesleff, Marja L MikkolaAbstract:Background: Foxi3 is a member of the large forkhead box family of transcriptional regulators, which have a wide range of biological activities including manifold developmental processes. Heterozygous mutation in Foxi3 was identified in several hairless dog breeds characterized by sparse fur coat and missing teeth. A related phenotype called hypohidrotic ectodermal dysplasia (HED) is caused by mutations in the ectodysplasin (Eda) pathway genes. Results: Expression of Foxi3 was strictly confined to the epithelium in developing ectodermal Appendages in mouse embryos, but no expression was detected in the epidermis. Foxi3 was expressed in teeth and hair follicles throughout embryogenesis, but in mammary glands only during the earliest stages of development. Foxi3 expression was decreased and increased in Eda loss- and gain-of-function embryos, respectively, and was highly induced by Eda protein in embryonic Skin explants. Also activin A treatment up-regulated Foxi3 mRNA levels in vitro. Conclusions: Eda and activin A were identified as upstream regulators of Foxi3. Foxi3 is a likely transcriptional target of Eda in ectodermal Appendage placodes suggesting that HED phenotype may in part be produced by compromised Foxi3 activity. In addition to hair and teeth, Foxi3 may have a role in nail, eye, and mammary, sweat, and salivary gland development. Developmental Dynamics 242:593–603, 2013. © 2013 Wiley Periodicals, Inc.
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TNF superfamily in Skin Appendage development.
Cytokine & Growth Factor Reviews, 2008Co-Authors: Marja L MikkolaAbstract:Abstract The development of Skin Appendages such as hairs, teeth, and mammary glands is regulated by signaling molecules of the Wnt, FGF, TGFβ, and Hedgehog pathways. Last decade has also revealed a pivotal role for the TNF family ligand ectodysplasin (Eda) in multiple steps of epithelial Appendage morphogenesis, from initiation to differentiation. Surprisingly, other members of the TNF superfamily such as Rank ligand, lymphotoxins, and TNF have recently been linked with specific aspects of Skin Appendage biology including branching of the mammary gland, hair shaft formation, and hair follicle cycling. This review focuses on the novel discoveries of Eda and other TNF related cytokines in Skin Appendage development made since the previous review on this topic in Cytokine and Growth Factor reviews in 2003.
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TNF superfamily in Skin Appendage development.
Cytokine & growth factor reviews, 2008Co-Authors: Marja L MikkolaAbstract:The development of Skin Appendages such as hairs, teeth, and mammary glands is regulated by signaling molecules of the Wnt, FGF, TGFbeta, and Hedgehog pathways. Last decade has also revealed a pivotal role for the TNF family ligand ectodysplasin (Eda) in multiple steps of epithelial Appendage morphogenesis, from initiation to differentiation. Surprisingly, other members of the TNF superfamily such as Rank ligand, lymphotoxins, and TNF have recently been linked with specific aspects of Skin Appendage biology including branching of the mammary gland, hair shaft formation, and hair follicle cycling. This review focuses on the novel discoveries of Eda and other TNF related cytokines in Skin Appendage development made since the previous review on this topic in Cytokine and Growth Factor reviews in 2003.
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p63 in Skin Appendage development.
Cell cycle (Georgetown Tex.), 2007Co-Authors: Marja L MikkolaAbstract:Development of Skin Appendages such as teeth, hairs and many exocrine glands, is regulated by inductive interactions between epithelial and mesenchymal tissues. At the molecular level, this interplay is mediated by conserved signaling proteins of the Wnt, FGF, TGFbeta, hedgehog and TNF families and executed by their downstream transcriptional regulators. p63, a transcription factor of the p53 family, is essential for the development of epidermis and its derivatives in vertebrates. The genomic organization of p63 is complex leading to transcription of at least six different isoforms with different, possibly even opposite functions. In humans, dominantly inherited mutations in p63 lead to a plenitude of syndromes that are featured by ectodermal dysplasia and/or craniofacial and limb malformations. In mice, lack of p63 causes a striking phenotype including severely truncated limbs, and absence of stratified epithelia and Skin derivatives including teeth, hair follicles and mammary, lacrimal and salivary glands. While the significance of p63 for the morphogenesis of Skin Appendages is obvious, the molecular pathways regulated by p63 are only now emerging. This review discusses the current knowledge on the role of p63 in Skin Appendage development with emphasis on teeth and hair follicles.
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Genetic basis of Skin Appendage development.
Seminars in cell & developmental biology, 2007Co-Authors: Marja L MikkolaAbstract:Morphogenesis of hair follicles, teeth, and mammary glands depends on inductive epithelial-mesenchymal interactions mediated by a conserved set of signalling molecules. The early development of different Skin Appendages is remarkably similar. Initiation of organogenesis is marked by the appearance of a local epithelial thickening, a placode, which subsequently invaginates to produce a bud. These early developmental stages require many of the same genes and signalling circuits and consequently alterations in them often cause similar phenotypes in several Skin Appendages. After the bud stage, these organs adopt diverse patterns of epithelial growth, reflected in the usage of more divergent genes in each.
Jian Sima - One of the best experts on this subject based on the ideXlab platform.
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eda activated relb recruits an swi snf baf chromatin remodeling complex and initiates gene transcription in Skin Appendage formation
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David SchlessingerAbstract:Ectodysplasin A (Eda) signaling activates NF-κB during Skin Appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in Skin Appendages, and epidermal knockout of BAF250a impairs Skin Appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
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Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in Skin Appendage formation.
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David SchlessingerAbstract:Ectodysplasin A (Eda) signaling activates NF-κB during Skin Appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in Skin Appendages, and epidermal knockout of BAF250a impairs Skin Appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
Hironobu Sasano - One of the best experts on this subject based on the ideXlab platform.
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sex steroid hormone receptors in human Skin Appendage and its neoplasms
Endocrine Journal, 2005Co-Authors: Yoshiyuki Kariya, Mariko Chiba, Mareyuki Endoh, Mika Watanabe, Kazuyuki Ishida, Takuya Moriya, Junji Takeyama, Takashi Suzuki, Hironobu SasanoAbstract:Sex steroids have been postulated to influence pathophysiology of human Skin through various Skin Appendages. The presence of sex steroid receptors has been also reported in adnexal tumors but its details still remained unknown. Therefore, in this study, we immunolocalized sex steroid receptor protein (estrogen receptor (ER)α, ERβ, progesterone receptor (PR)A, PRB and androgen receptor (AR)) in 23 cases of non-pathological Skin (male: 10, female: 13) and in 50 cases of Skin adnexal tumors (male 24, female 26; 38 benign and 12 malignant). ERα immunoreactivity was detected exclusively in basal cells of sebaceous glands of non-pathological Skin. AR and PRB immunoreactivity was detected in both differentiated and basal cells of sebaceous gland. AR and ERβ immunoreactivity was also detected in sebaceous and eccrine sweat glands but not in outer root sheath of hair follicles. In sebaceous gland neoplasms, the number of ERα positive cases was significantly lower in Skin Appendage neoplasms than non-pathological Skin. ERβ immunoreactivity was not detected in any of sebaceous gland neoplasms examined. There were no significant differences in PRA, PRB and AR immunoreactivity between non-pathological sebaceous gland and its neoplasm. In sweat gland neoplasms, the number of AR positive cases was significantly lower in benign neoplasms than their non-pathological counterpart. Therefore sex steroids are considered to play important roles in regulation of non-pathological Skin Appendage function and pathogenesis and/or development of its neoplasm. In addition, the status of the great majority of sex steroid hormone receptors was maintained throughout the process of neoplastic transformation of Skin Appendages, except for AR and ERα in sweat and sebaceous gland neoplasms.
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sex steroid hormone receptors in human Skin Appendage and its neoplasms
Endocrine Journal, 2005Co-Authors: Yoshiyuki Kariya, Mariko Chiba, Mareyuki Endoh, Mika Watanabe, Kazuyuki Ishida, Takuya Moriya, Junji Takeyama, Takashi Suzuki, Hironobu SasanoAbstract:Sex steroids have been postulated to influence pathophysiology of human Skin through various Skin Appendages. The presence of sex steroid receptors has been also reported in adnexal tumors but its details still remained unknown. Therefore, in this study, we immunolocalized sex steroid receptor protein (estrogen receptor (ER)alpha, ERbeta, progesterone receptor (PR)A, PRB and androgen receptor (AR)) in 23 cases of non-pathological Skin (male: 10, female: 13) and in 50 cases of Skin adnexal tumors (male 24, female 26; 38 benign and 12 malignant). ERalpha immunoreactivity was detected exclusively in basal cells of sebaceous glands of non-pathological Skin. AR and PRB immunoreactivity was detected in both differentiated and basal cells of sebaceous gland. AR and ERbeta immunoreactivity was also detected in sebaceous and eccrine sweat glands but not in outer root sheath of hair follicles. In sebaceous gland neoplasms, the number of ERalpha positive cases was significantly lower in Skin Appendage neoplasms than non-pathological Skin. ERbeta immunoreactivity was not detected in any of sebaceous gland neoplasms examined. There were no significant differences in PRA, PRB and AR immunoreactivity between non-pathological sebaceous gland and its neoplasm. In sweat gland neoplasms, the number of AR positive cases was significantly lower in benign neoplasms than their non-pathological counterpart. Therefore sex steroids are considered to play important roles in regulation of non-pathological Skin Appendage function and pathogenesis and/or development of its neoplasm. In addition, the status of the great majority of sex steroid hormone receptors was maintained throughout the process of neoplastic transformation of Skin Appendages, except for AR and ERalpha in sweat and sebaceous gland neoplasms.
Zhijiang Yan - One of the best experts on this subject based on the ideXlab platform.
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eda activated relb recruits an swi snf baf chromatin remodeling complex and initiates gene transcription in Skin Appendage formation
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David SchlessingerAbstract:Ectodysplasin A (Eda) signaling activates NF-κB during Skin Appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in Skin Appendages, and epidermal knockout of BAF250a impairs Skin Appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
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Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in Skin Appendage formation.
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David SchlessingerAbstract:Ectodysplasin A (Eda) signaling activates NF-κB during Skin Appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in Skin Appendages, and epidermal knockout of BAF250a impairs Skin Appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
