Developmental Regulation of Growth, Size and Shape

描述（由申请人提供）：如果器官可以从少量细胞中重新填充，这些细胞可以在生长过程中移除和替换其他细胞，在替换过程中保持组织尺寸，这将是潜在的优势。这种过程可能发生在发育过程中，称为“细胞竞争”。细胞竞争在昆虫发育、哺乳动物胚胎发生和肝脏再生过程中可见，并与肿瘤发育有关。当组织中含有具有不同生长特性的基因不同的细胞群时，“较强”的基因型可以完全消除“较弱”的基因型，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，并发现它取决于正常邻居对易感细胞的识别、吞噬和杀死。我们目前的目标是对识别和消除细胞的途径进行细胞和分子的理解，这些细胞如何成为去除的目标，当被靶向时如何发生凋亡，以及淘汰细胞被替换以保持组织形态的机制。由于细胞竞争在哺乳动物肝脏再生过程中发生，并与癌症有关，因此可以预期，基于这些研究，可以开发出抗肿瘤治疗和辅助人体器官再生的策略。细胞存活缺陷和细胞尸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、血管生成以及包括艾滋病毒/艾滋病、自身免疫性疾病和失明在内的传染病的基础。预计，如果有可能操纵细胞吞噬和杀死细胞之间生长差异的下游，可能会开发出不需要操纵癌基因或肿瘤抑制因子的策略来替代发育区室。

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.