Development and maintenance of plantar skin

摘要：掌足掌(足底和掌部)皮肤表皮增厚，表现为 独特的结构蛋白组合，有助于其卓越的抗病能力 生物力学应力。与邻近皮肤相比，PP皮肤的色素也较少， 无毛，汗腺(EG)密度高。前期研究 表明表皮的区域特异性分化强加于 角质形成细胞在胚胎/围产期发育期间，但一旦指定， 角质形成细胞对其起源部位产生内在的表观遗传记忆。嫁接和 文化实验表明，这种记忆是不完整的，而来自 原位真皮支持和增强适当的PP分化，同时信号 来自异位真皮可以促进选择性分化。这些研究一直是 受制于对一组有限的标记的依赖。这里提出的工作采用了 转基因小鼠将创造一个全面的分子描述唯一- 利用RNAseq技术进行特异的表皮分化并鉴定诱导信号 在发育过程中促进分化的真皮。可感应性损益 产生双背足和双腹足的基因的功能被用来探索这种程度 其中，指定鞋底区域角质形成细胞身份的诱导信号是 在成人体内维持特定部位的表皮分化所必需的。我们还要求 在完整的皮肤中操纵这些信号是否会在其他皮肤中刺激表皮 身体各部位采用足底表皮特征。成功完成 这项工作将解决关于固有角质形成细胞相对重量的争议 在完整的成人皮肤中，真皮的特征与正在进行的诱导信号。它是 旨在提供可能导致授予上级的新方法的见解 对被迫承担承重责任的患者皮肤的性能，用于 例如，当腿部截肢将此功能强加于更近端的肢体皮肤时。

Abstract: The thickened epidermis of palmoplantar (sole and palm) skin expresses a unique combination of structural proteins that contribute to its superior resistance to biomechanical stress. PP skin is also hypo-pigmented when compared with adjacent skin, is hairless and exhibits a high density of eccrine sweat glands (EG). Prior research demonstrates that regional specific differentiation of the epidermis is imposed on keratinocytes during embryonic/perinatal development but that once specified, keratinocytes develop an intrinsic epigenetic memory of their site of origin. Grafting and culture experiments suggest that this memory is incomplete, and that signaling from orthotopic dermis sustains and augments appropriate PP differentiation, while signals from heterotopic dermis can promote alternative differentiation. These studies have been hampered by reliance on a limited set of markers. The work proposed here employs genetically modified mice to create a comprehensive molecular description of sole- specific epidermal differentiation by RNAseq and identify inductive signals from the dermis that promote that differentiation during development. Inducible gain and loss of function of genes that generate bi-dorsal and bi-ventral feet are used to explore the extent to which the inductive signals that specify regional keratinocyte identity in the sole are required to maintain site-specific epidermal differentiation in the adult. We also ask whether manipulation of those signals in intact skin can provoke epidermis in other regions of the body to adopt aspects of sole epidermal character. Successful completion of this work will settle controversies about the relative weight of intrinsic keratinocyte characteristics vs. ongoing inductive signaling from dermis in intact adult skin. It is designed to provide insights that may lead to novel approaches to conferring superior performance on patient skin that has been forced to assume load-bearing duties, for example when leg amputation imposes this function on more proximal limb skin.