Development and maintenance of plantar skin

翻译后摘要：掌跖（鞋底和手掌）皮肤增厚的表皮表达了 独特的结构蛋白组合，有助于其上级抗性， 生物力学应力PP皮肤与邻近皮肤相比也是色素减退的， 无毛，外泌汗腺（EG）密度高。先前的研究 表明表皮的区域特异性分化被强加于 在胚胎/围产期发育期间的角质形成细胞， 角质形成细胞形成了其起源部位的内在表观遗传记忆。接枝和 培养实验表明，这种记忆是不完整的， 原位真皮维持并增强适当的PP分化，而信号 异位真皮的细胞分化可以促进替代分化。这些研究 由于依赖于有限的一组标记而受到阻碍。这里提出的工作采用 转基因小鼠，创造一个全面的分子描述的唯一- 通过RNAseq特异性表皮分化，并从表皮细胞中鉴定诱导信号。 在发育过程中促进分化真皮。诱导性增益和损失 产生双背足和双腹足的基因的功能被用来探索 在鞋底中指定局部角质形成细胞身份的诱导信号是 维持成人特定部位的表皮分化所需。我们还要求 在完整皮肤中操纵这些信号是否能刺激其他组织中的表皮， 身体的各个部位都具有独特的表皮特征。成功完成 这项工作将解决有关内在角质形成细胞相对重量的争议， 在完整的成人皮肤中，特征与来自真皮的正在进行的诱导信号传导。是 旨在提供见解，可能导致新的方法，赋予上级 在患者皮肤上的性能，已被迫承担承重责任， 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.