Theme B

主题B

• 批准号: 7908916
• 负责人: ANNE LEIGHTON CALOF
• 金额: $ 45.83万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7908916
• 关键词: Adopted; Apical; Cell Lineage; Cells; Connective Tissue; Development; Differentiation and Growth; Disease; Drosophila genus; Endocrine; Epithelial; Epithelial Cells; Epithelium; Faculty; Failure; Feedback; Growth; Informal Social Control; Larva; Malignant Neoplasms; Modeling; Morphogenesis; Nasal cavity; Neurons; Olfactory Epithelium; Output; Performance; Positioning Attribute; Process; Psoriasis; Research; Sensory; Signal Transduction; Smell Perception; Staging; Stem cells; Stereotyping; Stratified Epithelium; Surface; System; Systems Biology; Thick; Transforming Growth Factor beta; Vertebrates; Wing; animal tissue; base; imaginal disc; interest; morphogens; paracrine; tissue regeneration

Theme B: Epithelial Growth Control Theme Leader: Calof Other Faculty: Lander, Nie, Lowengrub, Wan, Mjolsness, Yu Background and Significance Epithelia are the fundamental building blocks of all animal tissues. They consist of sheets of closely packed cells with evident polarity along one axis (the apical-basal axis, orthogonal to the plane of the epithelium). Typically, epithelial cells are produced through stereotyped lineages, and cells at different lineage stages adopt different positions. Thus, in stratified (multilayered) epithelia, lineage stage often correlates with distance from the basal surface of the epithelium. Here we consider a performance objective common to many epithelia: precise self-regulation of growth and size. In a variety of experimental paradigms, epithelia seem to "know" when to stop growing, both during development and when participating in tissue regeneration. Failures in this process underlie diseases as diverse as psoriasis and cancer. A long-standing model of growth control is based on the notion of a simple paracrine (or endocrine) feedback loop, in which differentiated cells at the end of a lineage secrete a factor that inhibits the divisions of the progenitor cells that make them (Bullough, 1965). However, in deuterostomes (e.g. vertebrates), the growth and differentiation of epithelia is clearly also controlled by signals from underlying connective tissue, or stroma (Watt, 2001; Fuchs et al., 2004). The research described in Theme B focuses on growth control in two very different epithelia: the mammalian olfactory epithelium (OE)¿the sensory epithelium in the nasal cavity that contains neurons that transmit the sense of smell to the brain¿and the epithelium of the wing imaginal disc of the fruit fly Drosophila larva. In both cases, the fundamental question is the same: how does the system grow at the "right" rate, and stop growing when it reaches the "right" size? The context in which this question is asked, however, is very different in the two cases. In the OE, a stratified epithelium, the growth axis in question is apico-basal, i.e. we are interested in control of the thickness of the epithelium; in the wing disc the growth in question is in the plane of the epithelium, i.e. we are interested in the expansion of the epithelial sheet. Interestingly, we shall argue that critical factors in both cases are spatially-graded distributions of molecules belonging to the TGF-beta superfamily. In this sense, the problems discussed in this theme potentially overlap with the morphogen gradient problems of Theme A. However, the fact that the output of the systems discussed in this aim concerns proliferative dynamics gives them a distinctive character.

主题B：上皮增长控制 主题负责人：卡洛夫 其他教师：Lander，Nie，Lowengrub，Wan， Mjolsness，Yu 背景和意义 上皮是所有人的基本基础 动物组织。它们由密切的床单组成 沿着一个轴具有证据极性的填充细胞（该细胞 顶端轴，与该平面的正交 通常，产生上皮细胞 通过陈规定型的谱系和不同的细胞 血统阶段采用不同的位置。那，在 经常分层（多层）上皮，谱系阶段 与距离基本表面的距离相关 上皮。 在这里，我们考虑一个性能目标 对许多上皮：精确的增长自我调节 和大小。在各种实验范式中， 上皮似乎“知道”什么时候停止生长，两者都 在开发期间和参与组织时 再生。在此过程中失败的基础 像牛皮癣和癌症一样潜水的疾病。 长期存在的增长控制模型是基于 简单的旁分泌（或内分泌）的概念 反馈循环，其中末端分化了细胞 血统秘密的一个因素抑制分裂的因素 使它们成为它们的祖细胞（Bullough， 1965）。然而，在氘抑制中（例如 脊椎动物），生长和分化 上皮显然也受到信号的控制 基础连接的组织或基质（Watt，2001; Fuchs等，2004）。描述的研究 主题B非常关注两者的增长控制 不同的上皮：哺乳动物嗅觉 上皮（OE）»鼻中的感觉上皮 包含传递感官的神经元的空腔 气味向大脑和机翼的上皮 果蝇果蝇的想象盘。 在这两种情况下，基本问题都是相同的： 系统如何以“正确”的速率增长，并且 达到“正确”尺寸时停止增长？这 但是，问这个问题的上下文是 在两种情况下非常不同。 在OE中，分层上皮，生长轴 问题是apico-basal，即我们感兴趣 控制上皮厚度；在机翼 光盘的增长是在 上皮，即我们对扩展感兴趣 上皮纸。有趣的是，我们将争论 在两种情况下，关键因素均在空间分级 属于TGF-β的分子的分布 超家族。从这个意义上讲，讨论的问题 在这个主题中，可能与形态学重叠 主题A的梯度问题A。但是，事实 在此目标中讨论的系统的输出 关注激增的动态使他们有一个 独特的特征。