Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

利用自然进化的表型变异破译哺乳动物皮肤的位置调节密码

• 批准号: 10478147
• 负责人: Ricardo Mallarino
• 金额: $ 39.69万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478147
• 关键词: Anatomy; Biology; Biomedical Research; Code; Cutaneous; Development; Developmental Biology; Discipline; Disease; Embryo; Embryonic Development; Genetic; Genotype; Growth; Homeostasis; Individual; Laboratories; Laboratory mice; Lead; Link; Marsupialia; Membrane; Modeling; Molecular; Molecular Biology; Molecular Genetics; Morphology; Outcome; Pattern; Pattern Formation; Phenotype; Pigmentation physiologic function; Postdoctoral Fellow; Process; Regulator Genes; Research; Rodent; Science; Skin; System; Thick; Translating; Variant; Work; appendage; base; cell behavior; experimental study; functional genomics; gene regulatory network; genetic information; insight; interdisciplinary approach; post-doctoral training; postnatal; programs; regional difference; skin organogenesis; success; tool

Project summary My proposed research seeks to uncover the precise developmental mechanisms by which gene regulatory complexity is translated through cellular behaviors into specific morphological outcomes. Achieving this constitutes a fundamental challenge in biomedical sciences, as errors in embryonic patterning often lead to congenital and postnatal abnormalities that can have The mammalian skin displays marked anatomical variation in growth, thickness, pigmentation, and types of cutaneous appendages. These regional differences arise during embryogenesis, suggesting that gene regulatory networks controlling skin development harbor a latent reservoir of anatomical complexity. To understand how such regulatory complexity is translated into spatial patterns of cellular differentiation, drastic consequences for individuals. my research program combines the study of diverse, naturally occurring phenotypes in emerging model species, with parallel studies in the laboratory mouse, where powerful molecular and genetic tools already exist. The proposed experiments seek to elucidate how the skin acquires, interprets, and executes positional information by focusing on two distinct spatially patterned phenomena during skin development (1) stripe pattern formation in rodents, using a system I established as a postdoc and (2) formation of gliding membranes in marsupials, using a system under development in my laboratory. The approaches described in the two research programs integrate multiple disciplines, including developmental biology, molecular biology, evolutionary genetics, and functional genomics, with my expertise in skin developmental biology (postdoctoral training) and demonstrated success developing molecular tools in emerging model species (graduate and postdoctoral training). By focusing on developmental mechanisms, this work will uncover the stepwise processes by which genetic information generates spatial patterns of cellular differentiation during embryogenesis, provide a comprehensive roadmap for linking genotype and phenotype at an unprecedented mechanistic and conceptual level, and will generate fundamental insights into the biology of mammalian skin, from the processes controlling skin development and homeostasis to the mechanistic bases of diseased states.

项目总结