Mechanisms of signal transmission in vertebrate skin appendage development.

脊椎动物皮肤附属器发育中的信号传递机制。

• 批准号: 10612893
• 负责人: DAVID M PARICHY
• 金额: $ 35.53万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612893
• 关键词: Address; Affect; Animals; Attention; Basement membrane; Biological Assay; Biological Models; Biology; Birds; Cells; Chicken Model; Clinical; Complex; Coupled; Cues; Dedications; Dermal; Dermatology; Dermis; Development; Diffusion; Disease; Eccrine Glands; Ectodermal Dysplasia; Embryonic Development; Endowment; Epidermis; Epithelium; Etiology; Event; Experimental Models; Feathers; Fertilization; Fishes; Genetic; Gland; Hair; Health; Heritability; Human; Human Genetics; Image; Individual; Infrastructure; Inherited; Integumentary system; Lesion; Ligands; Link; Mammals; Mammary gland; Mediating; Medical; Mesenchymal; Methods; Microsurgery; Modality; Modeling; Molecular; Morphogenesis; NF-kappa B; Organ; Output; Pathway interactions; Pattern; Personal Satisfaction; Phenotype; Postembryonic; Reaction; Regenerative Medicine; Regulation; Research; Resolution; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Signaling Protein; Skin; Spatial Distribution; System; Testing; Time; Tissues; Tooth structure; Vertebrates; WNT Signaling Pathway; Work; Zebrafish; antagonist; appendage; cell behavior; cell motility; experimental study; extracellular; gene product; genetic analysis; genetic manipulation; in vivo; in vivo imaging; inhibitor; insight; meter; migratory population; molecular dynamics; mosaic; mouse model; novel; pharmacologic; skin disorder; skin fibrosis; skin organogenesis; teleost fish; therapy design; therapy development; transgene expression; transmission process; wound healing

PROJECT SUMMARY/ABSTRACT Skin appendages, including teeth, hair, eccrine and mammary glands, are conspicuous and medically impor- tant features of the human integument. Congenital and acquired disorders of skin appendages are common and frequently debilitating conditions. Although human genetic analyses and clinical dermatology have associ- ated numerous loci with skin appendage disorders, the molecular etiologies linking genetic lesions to human phenotypes in many cases remain obscure. Understanding molecular mechanisms that regulate skin ap- pendage patterning and morphogenesis in experimental model systems provides new avenues for developing therapies for skin disease. Indeed, research on chicken and mouse model systems has greatly advanced our understanding of the genetic regulation of skin appendage development and has already impacted clinical dermatology. Importantly, patterning cues, morphogenetic cell behaviors and the regulatory mechanisms that link them are conserved in zebrafish skin appendage development. Because skin appendages form superficial- ly in the transparent skin of developing fish, studying zebrafish skin patterning and morphogenesis enables in vivo analysis of cellular and molecular dynamics at resolutions not currently possible in other model systems. Studies in Aim 1 will contribute to our understanding of how the correct distribution of skin appendages is achieved by leveraging live imaging and conditional genetics to test the role of a novel population of migratory dermal cells likely to regulate skin appendage patterning. These studies will also uncover, for the first time, molecular mechanisms that govern dermal cell migration in intact vertebrate skin. Studies in Aim 2 will eluci- date mechanisms regulating the dynamic spatial distribution of signaling proteins known to be necessary for epithelial–mesenchymal interactions during early skin appendage morphogenesis in humans. By using condi- tional transgene expression to re-construct signaling networks in a zebrafish model of hereditary ectodermal dysplasia, these experiments will reveal mechanisms governing epithelial–mesenchymal signaling interactions at molecular resolution. Together, these studies will address some of the most important unanswered questions regarding skin appendage development and provide potential inroads to understanding the molecular etiology of human disorders affecting these tissues. 1

项目总结/文摘

项目成果

Transcriptomic profiling of tissue environments critical for post-embryonic patterning and morphogenesis of zebrafish skin.

• DOI: 10.7554/elife.86670
• 发表时间: 2023-09-11
• 期刊: eLife
• 影响因子: 7.7
• 作者: Aman AJ;Saunders LM;Carr AA;Srivatasan S;Eberhard C;Carrington B;Watkins-Chow D;Pavan WJ;Trapnell C;Parichy DM
• 通讯作者: Parichy DM