WNT Signals in Skin and Hair Development and Growth

皮肤和毛发发育和生长中的 WNT 信号

• 批准号: 9905919
• 负责人: Sarah E. Millar
• 金额: $ 37.29万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905919
• 关键词: Actins; Adherens Junction; Adult; Affect; Alleles; Area; Burn injury; Cell Adhesion; Cell Communication; Cell Maintenance; Cell Nucleus; Cells; Communication; Complex; Cytoskeleton; Data; Defect; Dermal; Development; Differentiation and Growth; Disease; Ectoderm; Embryo; Epidermis; Epithelial; Exhibits; FZD1 gene; Failure; Family member; Genetic; Genetic Transcription; Goals; Growth; Growth Disorders; Growth and Development function; Hair; Hair follicle structure; Hair shaft structure; Homeostasis; Image; In Vitro; Lead; Ligands; Maintenance; Mediating; Microfilaments; Mus; Mutation; Natural regeneration; Nuclear; Pathway interactions; Pattern; Phenotype; Play; Process; Reporter; Role; Signal Pathway; Signal Transduction; Skin; Skin Cancer; Specificity; Stem cells; Structure; Surface Ectoderm; TCF Transcription Factor; Testing; Therapeutic; Therapeutic Intervention; Time; Transgenic Organisms; WNT Signaling Pathway; Wnt proteins; Wound Healing; base; beta catenin; cell motility; cell type; design; in vivo; inhibitor/antagonist; keratinocyte; loss of function; mutant; new therapeutic target; novel; overexpression; paracrine; planar cell polarity; polarized cell; postnatal; receptor; response; skin organogenesis; transcription factor; tumor; tumorigenesis

DESCRIPTION (provided by applicant): Paracrine Wnt ligands participate in cell-cell communication by activating several different signaling pathways including the WNT/B-catenin pathway which stabilizes cytoplasmic b-catenin allowing it to enter the nucleus and activate transcription in partnership with LEF/TCF transcription factors, and non-canonical pathways that control epithelial planar cell polarity, the actin cytoskeleton, cell movements, and cell adhesion. These pathways can interact with each other, and perform critical functions in skin and hair follicle development and disease. However, the mechanisms by which signaling is limited and controlled to provide proper patterning of hair follicle development, and the ligands, receptors and downstream components that provide specificity to Wnt functions in the skin are incompletely identified. Delineating the components of these pathways and dissecting their mechanisms of action will be critical for developing strategies for skin and hair follicle regeneration in cases of congenital absence or loss, and for the treatment of hair growth disorders and epidermal tumors. To determine the mechanisms by which WNT/b-catenin signaling is controlled and patterned in the skin, uncover novel functions of non-canonical Wnt signaling, and identify receptors mediating these pathways, we will: (1) Identify secreted inhibitors that limit WNT/B-catenin pathway activity and pattern hair follicle development in embryonic skin; (2) Determine whether the non-canonical Wnt pathway components Daam1 and Daam2 act downstream of Wnt5a and control proliferation and hair follicle stem cell maintenance by regulating the actin cytoskeleton; (3) Test the hypothesis that the closely related Wnt receptors Fzd1 and Fzd2 mediate both b-catenin-dependent and non-canonical Wnt signaling pathways in developing and hair follicles and epidermis.