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

项目总结 我提出的研究试图揭示基因 调控的复杂性通过细胞行为转化为特定的形态 结果。实现这一点构成了生物医学科学的一个根本性挑战，因为错误 在胚胎模式中经常会导致先天性和后天的异常，这可能会 哺乳动物的皮肤显示出显著的解剖变异。 皮肤附属物的生长、厚度、色素沉着和类型。这些地区 差异出现在胚胎发育过程中，这表明基因调控网络控制着 皮肤发育蕴藏着解剖复杂性的潜在蓄水池。为了理解为什么会这样 调控的复杂性被转化为细胞分化的空间模式， 对个人造成严重后果。 我的研究 该计划结合了对新兴模式中各种自然发生的表型的研究 物种，在实验室小鼠中进行平行研究，在那里强大的分子和基因 工具已经存在。拟议中的实验试图阐明皮肤是如何获得的， 通过聚焦于两个不同的空间图案来解释和执行位置信息 皮肤发育过程中的现象(1)啮齿动物的条纹图案形成，使用系统I 建立为博士后和(2)有袋类动物滑膜的形成，使用一种系统 在我的实验室里正在研发。两个研究项目中描述的方法 综合多个学科，包括发育生物学、分子生物学、进化 遗传学和功能基因组学，凭借我在皮肤发育生物学方面的专业知识 (博士后培训)，并展示了在新兴模式下成功开发分子工具 物种(研究生和博士后培训)。通过关注发展机制，这一点 这项工作将揭示遗传信息产生空间的逐步过程 胚胎发育过程中的细胞分化模式提供了一个全面的路线图 在前所未有的机制和概念层面上将基因型和表型联系起来，并将 从这些过程中对哺乳动物皮肤的生物学产生基本的见解 控制皮肤发育和动态平衡，以达到疾病的机制基础。

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.