Serum Response Factor Controls Transcriptional Network Regulating Epidermal Function and Hair Follicle Morphogenesis Congxing Lin, Anna Hindes, Carole.

Slides:

Advertisements

Similar presentations

Plakoglobin as a Regulator of Desmocollin Gene Expression

Advertisements

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation

Expression of Frizzled Genes in Developing and Postnatal Hair Follicles Seshamma T. Reddy, Thomas Andl, Min-Min Lu, Edward E. Morrisey, Sarah E. Millar,

Activated Kras Alters Epidermal Homeostasis of Mouse Skin, Resulting in Redundant Skin and Defective Hair Cycling Anandaroop Mukhopadhyay, Suguna R.

Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation Daniela Weiland, Bent Brachvogel, Hue-Tran Hornig-Do,

Use of Induced Pluripotent Stem Cells in Dermatological Research

Expression of Frizzled Genes in Developing and Postnatal Hair Follicles Seshamma T. Reddy, Thomas Andl, Min-Min Lu, Edward E. Morrisey, Sarah E. Millar,

Sirpa Aho, Clive R. Harding, Jian-Ming Lee, Helen Meldrum, Carol A

Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment Dai-Jen Lee, Fei Du, Shih-Wei Chen, Manando Nakasaki, Isha Rana, Vincent.

CtBP1 Overexpression in Keratinocytes Perturbs Skin Homeostasis

The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle Leila J. Mady, Dare V. Ajibade, Connie Hsaio, Arnaud Teichert,

Jiang Chen, Christine Laclef, Alejandra Moncayo, Elizabeth R

Volume 16, Issue 10, Pages (May 2006)

Induction of Thymic Stromal Lymphopoietin Expression in Keratinocytes Is Necessary for Generating an Atopic Dermatitis upon Application of the Active.

Wanglong Qiu, Xiaojun Li, Hongyan Tang, Alicia S. Huang, Andrey A

Atypical Protein Kinase C Isoform, aPKCλ, Is Essential for Maintaining Hair Follicle Stem Cell Quiescence Shin-Ichi Osada, Naoko Minematsu, Fumino Oda,

Lack of the Vitamin D Receptor is Associated with Reduced Epidermal Differentiation and Hair Follicle Growth Zhongjion Xie, László Komuves, Qian-Chun.

Christina A. Young, Richard L

Matriptase Regulates Proliferation and Early, but Not Terminal, Differentiation of Human Keratinocytes Ya-Wen Chen, Jehng-Kang Wang, Fen-Pai Chou, Bai-Yao.

Impaired Skin Regeneration and Remodeling after Cutaneous Injury and Chemically Induced Hyperplasia in Taps-Transgenic Mice Maike Hildenbrand, Verena.

Skin-Specific Deletion of Mis18α Impedes Proliferation and Stratification of Epidermal Keratinocytes Koog Chan Park, Minkyoung Lee, Yoon Jeon, Raok Jeon,

Overexpression of Transcription Factor Ovol2 in Epidermal Progenitor Cells Results in Skin Blistering Briana Lee, Kazuhide Watanabe, Daniel Haensel,

Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder Chang-Yi Cui, Ryuga Ishii, Dean P. Campbell, Marc.

c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia

Frizzled6 Deficiency Disrupts the Differentiation Process of Nail Development Chang-Yi Cui, Joakim Klar, Patrik Georgii-Heming, Anne-Sophie Fröjmark,

Role of the Notch Ligand Delta1 in Embryonic and Adult Mouse Epidermis

Fatty Acid Transport Protein 1 Can Compensate for Fatty Acid Transport Protein 4 in the Developing Mouse Epidermis Meei-Hua Lin, Jeffrey H. Miner Journal.

Fate and Plasticity of the Epidermis in Response to Congenital Activation of BRAF Suguna R. Krishnaswami, Shantanu Kumar, Phillip Ordoukhanian, Benjamin.

Asifa S. Haider, Judilyn Duculan, Julia A. Whynot, James G. Krueger

Mohammad Rashel, Ninche Alston, Soosan Ghazizadeh

Fuz Controls the Morphogenesis and Differentiation of Hair Follicles through the Formation of Primary Cilia Daisy Dai, Huiping Zhu, Bogdan Wlodarczyk,

Enrique C. Torchia, Lei Zhang, Aaron J. Huebner, Subrata Sen, Dennis R

Establishment of Two Mouse Models for CEDNIK Syndrome Reveals the Pivotal Role of SNAP29 in Epidermal Differentiation Stina A. Schiller, Christina Seebode,

Stimulation of PPARα Promotes Epidermal Keratinocyte Differentiation In Vivo László G. Kömüves, Karen Hanley, Anne-Marie Lefebvre, Mao-Qiang Man, Dean.

Mitochondrial Function in Murine Skin Epithelium Is Crucial for Hair Follicle Morphogenesis and Epithelial–Mesenchymal Interactions Jennifer E. Kloepper,

Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis Ying Liu, Elizabeth R. Snedecor, Yeon.

Alexandra Charruyer, Lauren R. Strachan, Lili Yue, Alexandra S

Enpp2/Autotaxin in Dermal Papilla Precursors Is Dispensable for Hair Follicle Morphogenesis Laura Grisanti, Amelie Rezza, Carlos Clavel, Rachel Sennett,

Different Consequences of β1 Integrin Deletion in Neonatal and Adult Mouse Epidermis Reveal a Context-Dependent Role of Integrins in Regulating Proliferation,

Keratinocyte-Specific Deletion of the Receptor RAGE Modulates the Kinetics of Skin Inflammation In Vivo Julia S. Leibold, Astrid Riehl, Jan Hettinger,

Leah C. Biggs, Lindsey Rhea, Brian C. Schutte, Martine Dunnwald

Engineered Human Skin Substitutes Undergo Large-Scale Genomic Reprogramming and Normal Skin-Like Maturation after Transplantation to Athymic Mice Jennifer.

Increased Sensitivity of Histidinemic Mice to UVB Radiation Suggests a Crucial Role of Endogenous Urocanic Acid in Photoprotection Caterina Barresi,

Yuko Oda, Lizhi Hu, Vadim Bul, Hashem Elalieh, Janardan K

Transient Expression of Ephrin B2 in Perinatal Skin Is Required for Maintenance of Keratinocyte Homeostasis Gyohei Egawa, Masatake Osawa, Akiyoshi Uemura,

Wound Healing Is Defective in Mice Lacking Tetraspanin CD151

Thomas Andl, Seshamma T. Reddy, Trivikram Gaddapara, Sarah E. Millar

The Suppressor of Cytokine Signaling (SOCS)-3 Determines Keratinocyte Proliferative and Migratory Potential during Skin Repair Andreas Linke, Itamar.

Trangenic Misexpression of the Differentiation-Specific Desmocollin Isoform 1 in Basal Keratinocytes Frank Henkler, Molly Strom, Kathleen Mathers, Hayley.

Epidermal Stem Cells in the Isthmus/Infundibulum Influence Hair Shaft Differentiation: Evidence from Targeted DLX3 Deletion Jin-Chul Kim, Olivier Duverger,

Epidermal Inactivation of the Glucocorticoid Receptor Triggers Skin Barrier Defects and Cutaneous Inflammation Lisa M. Sevilla, Víctor Latorre, Ana Sanchis,

An Extended Epidermal Response Heals Cutaneous Wounds in the Absence of a Hair Follicle Stem Cell Contribution Abigail K. Langton, Sarah E. Herrick,

Barbara Marinari, Costanza Ballaro, Maranke I

Jaana Mannik, Kamil Alzayady, Soosan Ghazizadeh

Igfbp3 Modulates Cell Proliferation in the Hair Follicle

Development of an Ichthyosiform Phenotype in Alox12b-Deficient Mouse Skin Transplants Silvia de Juanes, Nikolas Epp, Susanne Latzko, Mareen Neumann,

The EGFR Is Required for Proper Innervation to the Skin

Expression of Activated MEK1 in Differentiating Epidermal Cells Is Sufficient to Generate Hyperproliferative and Inflammatory Skin Lesions Robin M. Hobbs,

Transcriptional Repression of miR-34 Family Contributes to p63-Mediated Cell Cycle Progression in Epidermal Cells Dario Antonini, Monia T. Russo, Laura.

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

Jonathan M. Lehman, Essam Laag, Edward J. Michaud, Bradley K. Yoder

Juan A. Pena, Jacqueline L. Losi-Sasaki, Jennifer L. Gooch

Persistent Transgene Expression and Normal Differentiation of Immortalized Human Keratinocytes In Vivo Gerald G. Krueger, Cynthia M. Jorgensen, Andrew.

Betacellulin Regulates Hair Follicle Development and Hair Cycle Induction and Enhances Angiogenesis in Wounded Skin Marlon R. Schneider, Maria Antsiferova,

Patched 1 and Patched 2 Redundancy Has a Key Role in Regulating Epidermal Differentiation Christelle Adolphe, Erica Nieuwenhuis, Rehan Villani, Zhu Juan.

Piyush Koria, Stelios T. Andreadis

Keratinocyte Differentiation in Hyperproliferative Epidermis: Topical Application of PPARα Activators Restores Tissue Homeostasis László G. Kömüves,

AP-1-Controlled Hepatocyte Growth Factor Activation Promotes Keratinocyte Migration via CEACAM1 and Urokinase Plasminogen Activator/Urokinase Plasminogen.

RXRα Ablation in Epidermal Keratinocytes Enhances UVR-Induced DNA Damage, Apoptosis, and Proliferation of Keratinocytes and Melanocytes Zhixing Wang,

Localized Inflammatory Skin Disease Following Inducible Ablation of I Kappa B Kinase 2 in Murine Epidermis Athanasios Stratis, Manolis Pasparakis, Doreen.

Presentation transcript:

Serum Response Factor Controls Transcriptional Network Regulating Epidermal Function and Hair Follicle Morphogenesis Congxing Lin, Anna Hindes, Carole J. Burns, Aaron C. Koppel, Alexi Kiss, Yan Yin, Liang Ma, Miroslav Blumenberg, Denis Khnykin, Frode L. Jahnsen, Seth D. Crosby, Narendrakumar Ramanan, Tatiana Efimova Journal of Investigative Dermatology Volume 133, Issue 3, Pages 608-617 (March 2013) DOI: 10.1038/jid.2012.378 Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Phenotypic and biochemical changes in Srf-cKO epidermis (epi). (a) Postnatal day 0 (P0) wild-type (wt) and mutant (mt) mice. (b) EOB phenotype, lack of whiskers, and abnormal hind limb digits in mutants. E18.5, embryonic day 18.5. (c) Acidic X-gal dye penetration assay. (d) Dehydration assay. Steady weight loss exhibited by mutants but not by wt control littermates, suggesting defective “inside-to-outside” barrier in mutants. (e) Immunoblot confirms serum response factor (SRF) ablation in mutant epidermis. Tubulin immunoblot verifies equal protein loading. (f) H&E and (g–m) immunofluorescent staining of E17.5 wt and mt littermate skin sections, using the indicated antibodies, color coded according to secondary antibodies. Secondary antibody alone was used as a negative control for each primary antibody (not shown). Nuclei were counterstained with Hoechst dye. βcat, β-catenin; der, dermis; Intβ4, integrin β4; Ker, keratin; Lor, loricrin. Bar=50μm. Journal of Investigative Dermatology 2013 133, 608-617DOI: (10.1038/jid.2012.378) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Abnormal expression of keratin 10, involucrin, and p63 in the epidermis of Srf-cKO mice. Immunohistochemical analysis of wild-type (wt) control and SRF-null mutant (mt) postnatal day 1 (P1) mouse skin sections for (a) keratin 10 and (b) involucrin expression. Positive staining is shown by brown staining. Secondary antibody alone was used as a control (No 1° Ab). Original magnification, × 40. (c) Immunofluorescent staining using antibodies specific for the indicated proteins in wt control and SRF-null mt P1 mouse skin sections. Secondary antibody alone was used as a negative control for each primary antibody (not shown). Nuclei were counterstained with Hoechst dye (DNA). Bar=50μm. Journal of Investigative Dermatology 2013 133, 608-617DOI: (10.1038/jid.2012.378) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Aberrant patterns of expression of the AP1 family members Fra-1, JunB and c-Jun, and C/EBPα transcription factors in epidermis (epi) lacking serum response factor. Immunofluorescence (upper panel) and immunohistochemical analyses of wild-type (wt) and Srf-cKO mutant (mt) E18.5 mouse skin sections for the expression of the indicated transcription factors. Nuclei were counterstained with Hoechst dye (upper panel). Positive staining for JunB, c-Jun, and C/EBPα is shown by brown staining. Secondary antibody alone was used as a negative control for each primary antibody (not shown). der, dermis. Bar=50μm. Journal of Investigative Dermatology 2013 133, 608-617DOI: (10.1038/jid.2012.378) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Engrafted serum response factor–null skin lacks hair but exhibits normal epidermal architecture and proper expression of differentiation markers. Wild-type (wt) and mutant (mt) E17.5 skins were engrafted onto the backs of nude mice. (a) General appearance of the grafts at the indicated days post grafting. (b) Histological and immunohistochemical analyses, using the indicated antibodies, of the 97-day (97-d) grafts. Positive staining is shown by brown staining. (c) Immunofluorescence analysis of TSLP expression. Secondary antibody alone was used as a negative control in both b and c (No 1° Ab). (d) TUNEL assay reveals no TUNEL-positive cells in the 97-d wt or mt grafts. In contrast, E17.5 mt sample used as a positive control shows numerous TUNEL-positive nuclei in epidermis. Nuclei were counterstained with Hoechst dye. d, days; Inv, involucrin; Ker, keratin; Lor, loricrin. (b–d) Bar=50μm. Journal of Investigative Dermatology 2013 133, 608-617DOI: (10.1038/jid.2012.378) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Changes in the expression of selected genes in serum response factor (SRF)–null epidermis. Selected genes (a) upregulated or (b) downregulated in mutant E17.5 epidermis, grouped into functional categories essential for skin barrier function. Numbers in parenthesis correspond to fold (a) increase or (b) decrease in Srf-cKO mutant versus wild-type (wt) control epidermis. P-value is less than 0.1. (c) Heat map shows both downregulation and upregulation of SRF target CArG-containing genes. A summary of SRF target genes, containing known and novel CArG sequences, generated using bioinformatics screen was published by Sun et al., 2006. About 60% of the putative SRF target genes have been functionally validated in that study. *Known CArG-containing SRF target genes, as reported in the aforementioned study. Journal of Investigative Dermatology 2013 133, 608-617DOI: (10.1038/jid.2012.378) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Serum response factor(SRF)–null E17.5 epidermis exhibits reduced expression of Lef1, Ptch1, and Shh. (a) Changes in the expression of selected genes linked to hair follicle morphogenesis in SRF-null E17.5 mouse epidermis. Numbers in parenthesis correspond to fold change in Srf-cKO mutant (mt) versus wild-type (wt) control epidermis; negative values represent fold decrease. Fold change>1.5, P-value cutoff: 0.1. (b, d, and e) 35S in situ hybridization on wt and mt E17.5 mouse skin sections using indicated probes. Nuclei were counterstained with Hoechst dye (blue). (c) Immunohistochemical analysis of wt and mt E17.5 mouse skin sections for Lef1 expression. Positive staining is shown by brown staining. Secondary antibody alone was used as a negative control for each primary antibody (not shown). (b–e) Bar=200μm. Journal of Investigative Dermatology 2013 133, 608-617DOI: (10.1038/jid.2012.378) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions