Microglial Crosstalk with Progenitors and Neurons during Retinal Neurogenesis

项目摘要 小胶质细胞是中枢神经系统的常驻免疫细胞，新出现的证据表明， 对发育中的大脑有影响。已经提出小胶质细胞调节增殖， 分化和各种系统中的神经元存活，但这些研究揭示了可变的，并且通常 矛盾的功能。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。目前，对小胶质细胞在发育中的功能知之甚少。 视网膜，尽管事实上，他们浸润神经视网膜在神经发生的发病和分布 贯穿增殖和新形成的分化层。我做了初步实验 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）调节新生神经元的存活。因此，我将区分 这两种可能性，然后确定涉及的信号通路。完成这项工作将导致 这是第一个研究小胶质细胞的功能和表型在发育中的哺乳动物视网膜，并将确定 小胶质细胞是否对视网膜的正常发育至关重要。此外，这项建议将扩大我们的 目前对小胶质细胞和祖细胞/神经元之间串扰的理解， 这些细胞在皮质发育、成人神经发生和干细胞治疗中的复杂作用。

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.