Control of symmetric cell division by the spindle assembly factor HMMR

组织的生长和发育涉及组织内细胞与其局部环境（包括细胞外基质）之间的相互作用。组织中的细胞必须平衡生长和死亡，这两个复杂的过程是由环境提供的线索控制的。透明质酸是一种ECM成分，它吸收组织中的水分，但也与细胞表面受体结合，促进细胞的生长和运动。由于其补水特性，透明质酸有许多商业用途，包括美容应用，但它也是维持和分化某些干细胞所需要的。有趣的是，我们发现透明质酸介导的运动受体（HMMR）是少数确定的透明质酸受体之一，实际上是一种调节细胞生长的中心体和微管相关蛋白。今天，我们并不完全知道HMMR如何调节细胞生长或它如何影响透明质酸信号传导。此外，我们还不知道这些潜在的函数是分开的还是相连的。这项研究计划的长期目标是更好地理解控制干细胞细胞分裂的分子和机制。本研究的短期目标是确定HMMR在细胞生长过程中控制的过程。最重要的假设是，HMMR调节基于微管的过程，而不是透明质酸结合所需要的。为了实现我们研究计划的长期目标，本提案概述了研究方法，将解决未来五年的三个具体目标：了解HMMR如何调节细胞分裂的方式和每次分裂产生的后代细胞的大小。2. 确定HMMR是否需要作为透明质酸介导信号事件的受体。3. 使用在特定组织中缺乏Hmmr的小鼠来确定在组织发育和维持过程中祖细胞生长过程中对Hmmr的需求。麦克斯韦实验室的专业知识在于我们对HMMR的研究，我们有许多独特的模型来研究HMMR生物学。我们预期这项研究计划会带来一些好处。我们将确定一个假定的受体对重要的ECM成分的贡献。此外，我们将对组织特异性干细胞分裂和维持上皮组织完整性的机制产生分子见解。

The growth and development of a tissue involves interaction between the cells in the tissue and their local environment, including the extracellular matrix (ECM). Cells in a tissue must balance growth with death and these two complex processes are controlled by cues provided by their environment. Hyaluronan is an ECM component that absorbs water in the tissue but also engages surface receptors on cells to promote their growth and movement. Due to its hydrating nature, hyaluronan has many commercial uses, including cosmetic applications, but it is also needed for the maintenance and differentiation of certain stem cells. Interestingly, we have found that hyaluronan mediated motility receptor (HMMR), one of few defined receptors for hyaluronan, is in fact a centrosome and microtubule-associated protein that regulates cell growth. Today, we do not fully know how HMMR regulates cell growth or how it might affect hyaluronan signaling. Moreover, we do not yet know if these potential functions are separate or connected. The long term goal for the proposed research program is to better understand the molecules and mechanisms that control cell division in stem cells. The short term goal for the proposed research is to determine the processes controlled by HMMR during cell growth. The overarching hypothesis is that HMMR regulates microtubule-based processes and is not needed for hyaluronan binding. To move towards the long term goal of our research program, this proposal outlines research methodologies that will address three specific objectives in the next five years: 1. Understand how HMMR regulates the way cells divide and the size of the progeny cells that are produced by each division. 2. Determine whether HMMR is needed as a receptor for hyaluronan to mediate signaling events. 3. Use mice that are deficient for Hmmr in a specific tissue to determine the need for HMMR during the growth of progenitor cells during tissue development and maintenance in vivo. The expertise in the Maxwell lab lies in our studies of HMMR and we have a number of unique models to study HMMR biology. We anticipate several benefits from the research program. We will determine the contributions of a putative receptor to a vital ECM component. In addition, we will generate molecular insights into the mechanisms by which tissue-specific stem cells divide and maintain the integrity of epithelial tissue.