Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2):a008029. doi: 10.1101/cshperspect.a008029.
The skin and its appendages constitute the largest organ of the body. Its stratified epithelia offer protection from environmental stresses such as dehydration, irradiation, mechanical trauma, and pathogenic infection, whereas its appendages, like hair and sebaceous glands, help regulate body temperature as well as influence animal interaction and social behavior through camouflage and sexual signaling. To respond to and function effectively in a dynamic external environment, the skin and its appendages possess a remarkable ability to regenerate in a carefully controlled fashion. When this finely tuned homeostatic process is disrupted, skin diseases such as cancers may result. At present, the molecular signals that orchestrate cell proliferation, differentiation, and patterning in the skin remain incompletely understood. It is increasingly apparent that many morphogenetic pathways with key roles in development are also important in regulating skin biology. Of these, Wnt signaling has emerged as the dominant pathway controlling the patterning of skin and influencing the decisions of embryonic and adult stem cells to adopt the various cell lineages of the skin and its appendages, as well as subsequently controlling the function of differentiated skin cells. Here we will review established concepts and present recent advances in our understanding of the diverse roles that Wnt signaling plays in skin development, homeostasis, and disease.
皮肤及其附属物构成了人体最大的器官。其分层上皮提供了对环境压力的保护，如脱水、辐射、机械创伤和病原感染，而其附属物，如毛发和皮脂腺，有助于通过伪装和性信号来调节体温以及影响动物的相互作用和社会行为。为了对外界动态环境做出反应并有效地发挥作用，皮肤及其附属物具有以精细控制的方式进行再生的显著能力。当这种精细的动态平衡过程被打乱时，就会导致皮肤疾病，如癌症。目前，调节皮肤中细胞增殖、分化和模式形成的分子信号仍不完全清楚。越来越明显的是，许多在发育中具有关键作用的形态发生途径对于调节皮肤生物学也很重要。其中，Wnt 信号转导已成为控制皮肤模式形成的主要途径，并影响胚胎和成年干细胞做出的各种决定，使其采用皮肤及其附属物的各种细胞谱系，随后控制分化皮肤细胞的功能。在这里，我们将回顾已确立的概念，并介绍我们对 Wnt 信号转导在皮肤发育、动态平衡和疾病中的多种作用的最新理解。
