RUI: Adult neurogenesis: precursor cell regulation and replenishment

许多脊椎动物和无脊椎动物，包括人类，在整个生命过程中保留了制造新神经元的能力，并将这些神经元纳入成年大脑的回路中。这种成年神经发生的过程发生在小龙虾的大脑中，通过一个系统，具有许多与高等脊椎动物相同的特征，这表明在成年大脑中产生新神经元的共同策略。然而，小龙虾大脑中的神经元前体细胞在空间上是分离的，从而可以研究该谱系的特定成分。这种组织和小龙虾系统的其他方面提供了独特的机会来探索导致成年神经元产生的细胞和分子事件的顺序。在小龙虾的大脑中，第一代前体细胞（神经干细胞）不是自我更新的，而是从外部来源补充到它们的生态位。体外实验表明造血系统是这些细胞的来源之一。本研究的目的是：（1）探索第一代神经元前体细胞的结构和功能调控;（2）研究内源性和环境因素对前体细胞谱系的影响;（3）利用延时细胞跟踪技术，在真实的时间内探索血细胞与微生态位之间的吸引机制。如果这些研究证实了血细胞和神经干细胞之间的关系，预计该项目将对我们理解神经系统发育和进化的机制产生深远的影响。这些研究的主要影响将是进一步定义神经干细胞的起源和功能，促进在进化背景下重新审视造血系统和神经系统之间的关系，并培养大量的本科生作为下一代年轻的神经科学家。

Many vertebrate and invertebrate organisms, including humans, retain the ability to make new neurons throughout life and to incorporate these into circuits in the adult brain. This process of adult neurogenesis occurs in the crayfish brain via a system that has many features in common with higher vertebrates, suggesting a common strategy for the generation of new neurons in adult brains. However, neuronal precursor cells in the crayfish brain are spatially separated, allowing studies on specific components of the lineage. This organization and other aspects of the crayfish system provide unique opportunities to explore the sequence of cellular and molecular events leading to the production of adult-born neurons. In the crayfish brain, first-generation precursors (neuronal stem cells) are not self-renewing, but instead are replenished from a source external to their niche. In vitro experiments suggest the hematopoietic (blood-producing) system as one source of these cells. This proposal will, (1) explore the structure and functional regulation of the first-generation neuronal precursor cells; (2) examine the influence of endogenous and environmental agents on the precursor lineage; and (3) probe the attraction mechanisms between blood cells and the niche in real time with time-lapse cell tracking. If a relationship between blood cells and neuronal stem cells is confirmed by these studies, it is anticipated that this project will have profound implications on our understanding of the mechanisms responsible for the development and evolution of the nervous system. The primary impact of these studies will be to define further the origins and function of neuronal stem cells, to promote a re-examination of the relationship between the hematopoietic and nervous systems in an evolutionary context, and to train numerous undergraduate students as the next generation of young neuroscientists.