Inductive properties of the dermal papilla of the hair follicle

毛囊真皮乳头的感应特性

• 批准号: 8703500
• 负责人: BRUCE A MORGAN
• 金额: $ 37.22万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-05 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703500
• 关键词: Ablation; Address; Adult; Behavior; Biological Models; Cell Count; Cell Death; Cell Size; Cells; Cellularity; Characteristics; Collaborations; Dermal; Emotional; Epithelial; Epithelial Cells; Epithelium; Frequencies; Gene Expression; Genes; Graafian Follicles; Growth; Hair; Hair Part; Hair bulb structure; Hair follicle structure; Hair shaft structure; In Vitro; Individual; Maintenance; Mediating; Mesenchymal; Mesenchyme; Methods; Molds; Morphogenesis; Morphology; Mouse Strains; Mus; Natural regeneration; Organ; Organ Size; Organism; Organogenesis; Pattern Formation; Phenotype; Platelet-Derived Growth Factor; Population; Prevention; Probability; Process; Production; Property; Recruitment Activity; Regenerative Medicine; Regulation; Research; Role; Shapes; Signal Pathway; Signal Transduction; Skin; Specific qualifier value; Stem cells; Structure; System; Testing; Time; To specify; Transgenic Organisms; Wild Type Mouse; Work; adult stem cell; cell type; critical period; gain of function; gain of function mutation; in vivo; insight; keratinocyte; progenitor; psychologic; research study; restoration; stem cell biology; stem cell population; tongue papilla; tool; transcription factor

DESCRIPTION (provided by applicant): The hair follicle has emerged as an important focus of research not only because of the psychological and emotional impacts of hair loss or excessive hair growth, but also because the hair follicle is periodically regenerated from a resident stem cell population in the adult and this serves an important model system in stem cell biology, regenerative medicine, and organogenesis. The hair follicle is composed of two principle components, (1)an epithelial population that comprises the majority of the follicle and gives rise to the differentiated cells that form the hair shaft and its surrounding cell layers in the follicl, and (2) a specialized mesenchymal population, the dermal papilla, that guides the activities of these epithelial cells. We have developed methods to manipulate gene expression specifically in the dermal papilla of the hair follicles after they have formed and exploited these to study the signaling between the dermal papilla and the follicular epithelium. This has provided insight onto signals that impinge on DP cells to control the production of signals that in turn regulate keratinocyte behavior and hair growth. These experiments suggest a second mechanism dictating the size and shape of the hair produced that occurs through active and dynamic regulation of the number of DP cells per follicle. The size of the hair correlates with the number of DP cells /follicle. One aim of this research is to test the significance of this correlation by selectively ablating DP cells in adult hair follicles and evaluating both the effects on hair growt and cycling as well as mechanisms that may compensate for cell death in the DP compartment. A second is to characterize the role of a transcription factor, Sox2 that is expressed in the DP. The phenotypes we observe after deleting the Sox2 gene specifically in the DP suggests it acts to regulate DP size during a critical period in follicular regeneration. We will test this hypothess with gain of function and rescue experiments and identify the gene expression changes that mediate Sox2 function in the DP. Signals within and between follicles, as well as from surrounding cell types in the skin all contribute to specifying DP size. To characterize those signals, we will extend our studies using DP specific blockade of additional signaling pathways to characterize how they contribute to these two mechanisms, signal production per DP cell and regulation of DP cell number. Successful completion of this work will provide insight into the mechanisms by which a progenitor pool interacts with and molds its niche and how that niche contributes to the regulation organ size and shape in the context of the changing needs of the organism.

描述（由申请人提供）：毛囊已经成为研究的重要重点，这不仅是因为脱发或过度毛发的心理和情感影响，还因为毛囊是从成人的居民干细胞中定期再生的，这在成年人的居民干细胞中再生，这在干细胞生物学，再生医学和机构中都具有重要的模型系统。毛囊由两个原理成分组成，（1）上皮种群，其中包括大多数卵泡，并引起形成毛发轴及其周围细胞层的分化细胞，（2）一种专业的中质群群体，具有这些上皮细胞活性。我们已经开发了在毛囊的真皮乳头上特别操纵基因表达的方法，并在它们形成并利用它们以研究真皮乳头和卵泡上皮之间的信号传导。这为构成了DP细胞的信号的见解，以控制信号的产生，而信号反过来又调节角质形成细胞的行为和头发生长。这些实验表明，第二种机制决定了通过每个卵泡的DP细胞数量的主动和动态调节产生的头发的大小和形状。头发的大小与DP细胞 /卵泡的数量相关。这项研究的目的是通过选择性地烧毁成人毛囊中的DP细胞来测试这种相关性的重要性，并评估对头发生长和循环的影响以及可能补偿DP室中细胞死亡的机制。第二是表征DP中表达的转录因子SOX2的作用。我们在DP中特别删除SOX2基因后观察到的表型表明，在卵泡再生的关键时期，它起作用可调节DP大小。我们将通过功能和救援实验的获取来检验该假设，并确定介导DP中SOX2功能的基因表达变化。卵泡内和之间的信号以及皮肤中周围细胞类型的信号都有助于指定DP大小。为了表征这些信号，我们将使用DP特定的其他信号通路的封锁扩展研究，以表征它们如何贡献这两种机制，每个DP细胞的信号产生以及DP细胞数的调节。成功完成这项工作将洞悉祖细胞池与其利基市场相互作用并塑造其利基市场的机制，以及该利基在不断变化的有机体需求的背景下如何促进调节器官的大小和形状。