Maintenance and Repair of the C. elegans Skin

摘要 皮肤是动物与外部环境之间的主要界面 环境。皮肤在有机体的整个生命过程中保持其结构的完整性。 同时对外部挑战提供被动和主动的防御。而当 近年来，对皮肤发育的了解进展迅速，但知之甚少 成熟的皮肤是如何在成年生活中保持的，包括它如何愈合伤口。更多 总的来说，维持成熟组织的机制仍然相对较差。 明白了。这项研究计划的总体目标是在分子水平上理解 如何在成人生活中修复和维护简单的皮肤层。这一制度 选择的是线虫的皮肤，一种比较简单和实验性的 易于处理的皮肤层模型。线虫的皮肤由简单的表皮组成 上皮和相关的基底层和根尖细胞外基质，基底 膜和角质层。先前的研究表明，成熟的皮肤对损伤有怎样的反应 并自我修复。这项工作导致了成人皮肤基因调节器的发现 维护；这些基因的功能丧失不会影响皮肤发育，但会导致 在进行性成人起病的成人皮肤退化。未来的研究将会延伸 这些方法解剖了成熟的表皮是如何在正常和 令人不安的条件。皮肤的表皮和细胞外基质起着 生物发生、维护和修复一体化单元。拟议的工作还将 研究表皮和细胞外基质在组织中是如何沟通的 维护和伤口修复。这些研究还将讨论一个 细胞外基质脂质层在皮肤通透性屏障的形成和修复中起作用。这个 由此得到的见解应该会促进与几个方面相关的皮肤生物学的知识 人类健康，包括正常的伤口愈合，慢性伤口，和皮肤纤维化 肥厚性疤痕。

Summary The skin is the primary interface between animals and their external environment. The skin maintains its structural integrity throughout the life of an organism while providing passive and active defenses against external challenges. While understanding of skin development has advanced rapidly in recent years, less is known of how the mature skin is maintained in adult life, including how it heals wounds. More broadly, the mechanisms that maintain mature tissues are still relatively poorly understood. The overall goal of this research program is to understand at the molecular level how a simple skin layer is repaired and maintained during adult life. The system of choice is the skin of the nematode C. elegans, a relatively simple and experimentally tractable model for skin layers. The C. elegans skin comprises a simple epidermal epithelium and associated basal and apical extracellular matrices, the basement membrane and the cuticle. Previous studies have how the mature skin responds to injury and repairs itself. This work led to the discovery of genetic regulators of adult skin maintenance; loss of function in such genes does not affect skin development but results in progressive adult-onset degeneration of the adult skin. Future studies will extend these approaches to dissect how the mature epidermis is maintained in normal and perturbed conditions. The epidermis and extracellular matrices of the skin function as an integrated unit in biogenesis, maintenance and repair. The proposed work will also investigate how the epidermis and extracellular matrix communicate in tissue maintenance and wound repair. These studies will also address the roles of an extracellular matrix lipid layer in formation and repair of the skin permeability barrier. The resulting insights should advance knowledge of skin biology relevant to several aspects of human health, including normal wound healing, chronic wounds, and skin fibrosis in hypertrophic scarring.