Microglial Crosstalk with Progenitors and Neurons during Retinal Neurogenesis

视网膜神经发生过程中小胶质细胞与祖细胞和神经元的串扰

基本信息

批准号：
9191700
负责人：
Sarah Rose Anderson
金额：
$ 4.08万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-16 至 2018-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9191700
关键词：
Address Adult Affect Amacrine Cells Attenuated Biological Models Blocking Antibodies Brain Bromodeoxyuridine CSF1 gene Cell Cycle Cell Death Cell Proliferation Cells Cerebral cortex Cessation of life Cleaved cell Complex Cone Development Disease Embryo Generations Health Image Immune Influentials Injury Knock-out Light Mediating Microglia Minocycline Modeling Monitor Nervous System Physiology Neural Retina Neuraxis Neurons Participant Pathway interactions Phagocytosis Phenotype Process Production Proliferating Proteins Retina Retinal Retinal Ganglion Cells Role Shapes Signal Pathway Signal Transduction Stem cell transplant System TNF gene Testing Work adult neurogenesis cell type direct application macrophage nerve stem cell nervous system disorder neurogenesis neuronal survival newborn neuron novel postnatal progenitor receptor research study retinal neuron retinal progenitor cell stem cell therapy transcriptome sequencing visual process visual processing

项目摘要

Project Summary Microglia are the resident immune cells of the central nervous system and emerging evidence suggests they are influential in shaping the developing brain. Microglia have been proposed to regulate proliferation, differentiation, and neuronal survival in various systems but these studies reveal variable, and often contradictory, functions. Utilizing the simplicity of the embryonic mammalian retina, we can directly assess the role of microglia in regulating neurogenesis. Currently, little is known about microglial function in the developing retina, despite the fact that they infiltrate the neural retina at the onset of neurogenesis and distribute throughout proliferating and newly forming differentiated layers. I have performed preliminary experiments addressing this, and the results suggest that microglia either 1) directly modulate retinal progenitor proliferation and differentiation, or 2) regulate the survival of newly born neurons. Therefore, I will differentiate between these two possibilities, and then identify the signaling pathways involved. Completion of this work will result in the first study of microglial function and phenotype in the developing mammalian retina, and will determine whether microglia are crucial for proper development of the retina. In addition, this proposal will expand on our current understanding of crosstalk between microglia and progenitors/neurons that will shed light on the complex role for these cells in cortical development, adult neurogenesis, and stem cell therapies.

项目摘要小胶质细胞是中枢神经系统的常驻免疫细胞，新兴的证据表明它们是在塑造发展中的大脑方面具有影响力。已经提出小胶质细胞来调节增殖，在各种系统中的分化和神经元生存率矛盾，功能。利用胚胎哺乳动物视网膜的简单性，我们可以直接评估小胶质细胞在调节神经发生中的作用。当前，关于开发中的小胶质函数知之甚少视网膜，尽管事实上它们在神经发生发作时浸润神经视网膜在整个增殖和新形成的区分层。我已经进行了初步实验解决这个问题，结果表明小胶质细胞1）直接调节视网膜祖细胞增殖和分化，或2）调节新生神经元的生存。因此，我将区分这两种可能性，然后确定所涉及的信号通路。完成这项工作将导致在发育中的哺乳动物视网膜中的小胶质功能和表型的首次研究，将确定小胶质细胞是否对于视网膜的正常发展至关重要。此外，该提议将扩大我们的当前对小胶质细胞和祖细胞/神经元之间的串扰的理解，这些会揭示这些细胞在皮质发育，成人神经发生和干细胞疗法中的复杂作用。