Control of symmetric cell division by the spindle assembly factor HMMR

组织的生长和发育涉及组织中的细胞与其局部环境（包括细胞外基质（ECM））之间的相互作用。组织中的细胞必须平衡生长和死亡，这两个复杂的过程由环境提供的线索控制。 Hybryonan是一种ECM成分，它吸收组织中的水，但也与细胞上的表面受体结合，以促进细胞的生长和运动。由于其水合性质，透明质酸具有许多商业用途，包括化妆品应用，但它也需要某些干细胞的维持和分化。有趣的是，我们发现透明质酸介导的运动受体（HMMR），透明质酸的少数定义的受体之一，实际上是一个中心体和微管相关蛋白，调节细胞生长。今天，我们不完全知道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，我们还不知道这些势函数是分离的还是连接的。 该研究计划的长期目标是更好地了解控制干细胞细胞分裂的分子和机制。这项研究的短期目标是确定细胞生长过程中HMMR控制的过程。总体假设是HMMR调节基于微管的过程，并且不需要透明质酸结合。为了实现我们研究计划的长期目标，该提案概述了未来五年将实现三个具体目标的研究方法： 1.了解HMMR如何调节细胞分裂的方式以及每次分裂产生的子代细胞的大小。 2.确定是否需要HMMR作为透明质酸的受体来介导信号传导事件。 3.使用在特定组织中缺乏Hmmr的小鼠来确定在体内组织发育和维持期间祖细胞生长期间对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。我们预计从研究计划中获得一些好处。我们将确定一个假定的受体的重要ECM成分的贡献。此外，我们将产生组织特异性干细胞分裂和维持上皮组织完整性的机制的分子见解。

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.