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）：毛囊已成为研究的重要焦点，不仅是因为脱发或毛发过度生长的心理和情感影响，而且还因为毛囊定期从成人的常驻干细胞群再生，这是干细胞生物学，再生医学和器官发生中的重要模型系统。毛囊由两个主要成分组成，（1）上皮细胞群，其包括毛囊的大部分并产生形成毛囊中的毛干及其周围细胞层的分化细胞，以及（2）特化的间充质细胞群，即真皮乳头，其引导这些上皮细胞的活动。我们已经开发出方法来操纵基因表达，特别是在毛囊的毛乳头后，他们已经形成，并利用这些研究毛乳头和毛囊上皮之间的信号。这提供了对影响DP细胞的信号的了解，以控制信号的产生，进而调节角质形成细胞的行为和毛发生长。这些实验表明，通过对每个毛囊的DP细胞数量的主动和动态调节，产生了决定毛发大小和形状的第二种机制。毛发的大小与DP细胞/毛囊的数量相关。本研究的一个目的是通过选择性消融成年毛囊中的DP细胞并评估对毛发生长和周期的影响以及可能补偿DP隔室中细胞死亡的机制来测试这种相关性的意义。第二个是表征DP中表达的转录因子Sox 2的作用。我们观察到的表型后删除的Sox 2基因，特别是在DP表明它的行为，以调节DP的大小在卵泡再生的关键时期。我们将通过功能获得和拯救实验来验证这一假设，并确定在DP中介导Sox 2功能的基因表达变化。毛囊内和毛囊之间的信号以及来自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特异性阻断其他信号传导途径来扩展我们的研究，以表征它们如何有助于这两种机制，每个DP细胞的信号产生和DP细胞数量的调节。这项工作的成功完成将提供深入了解祖池与其生态位相互作用和塑造其生态位的机制，以及该生态位如何在生物体不断变化的需求背景下有助于调节器官大小和形状。