Developmental Regulation of Growth, Size and Shape

描述(申请人提供)：如果器官可以由少量细胞重新填充，在生长过程中移除和替换其他细胞，并在替换过程中保持组织尺寸，这将是潜在的优势。这样的过程可以发生在发育过程中，在那里它被称为“细胞竞争”。细胞竞争见于昆虫发育、哺乳动物胚胎发育和肝脏再生，并与肿瘤的发展有关。当组织包含具有不同生长特性的遗传上不同的细胞群体时，“强”型可以完全消除“弱”型，并填满整个隔室。我们已经确定了细胞竞争所需的16个基因，并发现它依赖于正常邻居对敏感细胞的识别、吞噬和杀死。我们目前的目标是了解识别和消除细胞的途径，这些细胞是如何成为去除的目标，并在这样的靶向下经历凋亡，以及取代竞争对手的细胞以保持组织形态的机制。由于细胞竞争发生在哺乳动物肝脏再生过程中，并与癌症有关，预计抗肿瘤治疗和协助人体器官再生的策略可以基于这些研究。细胞存活缺陷和细胞身体吞噬是神经退行性疾病、神经元损伤、心脏病发作、中风、动脉粥样硬化、血管生成以及艾滋病毒/艾滋病、自身免疫性疾病和失明等感染性疾病的基础。预计，如果证明有可能操纵细胞吞噬和杀死细胞之间生长差异的下游，可能会开发出替代不需要操纵癌基因或肿瘤抑制因子的发育间隔的策略。

DESCRIPTION (provided by applicant): It would be potentially advantageous if organs could be repopulated from a small number of cells that would remove and replace other cells during growth, preserving tissue dimensions during the replacement. Such a process can occur during development, where it is called "cell competition". Cell competition is seen during insect development, mammalian embryogenesis, and liver regeneration, and implicated in tumor development. When tissues contain genetically distinct cell populations with different growth properties, the `stronger' genotype can completely eliminate the `weaker' genotype and come to fill the entire compartment. We have identified 16 genes that are required for cell competition, and found that it depends on recognition, engulfment and killing of susceptible cells by their normal neighbors. Our current goal is a cellular and molecular understanding of the pathways that recognize and eliminate cells, how such cells become targets for removal, and undergo apoptosis when so targeted, and the mechanisms by which out-competed cells are replaced to preserve tissue morphology. As cell competition occurs during mammalian liver regeneration, and is implicated in cancer, it is anticipated that anti-tumor therapies and strategies to assist regeneration of human organs can be based on these studies. Defective cell survival and cell corpse engulfment underlie neurodegenerative diseases, neuronal injuries, heart attack, stroke, atherosclerosis, angiogenesis, and infectious diseases including HIV/AIDS, autoimmune diseases, and blindness. It is anticipated that, should it prove possible to manipulate cell engulfment and killing downstream of growth differences between cells, strategies may be developed for the replacement of developmental compartments that do not require manipulating oncogenes or tumor suppressors.