RUI: Adult neurogenesis: precursor cell regulation and replenishment

许多脊椎动物和无脊椎生物，包括人类在内，在整个生命过程中都保持着制造新神经元的能力，并将这些神经元整合到成人大脑的回路中。在小龙虾的大脑中，成年神经发生的过程是通过一个与高等脊椎动物有许多共同特征的系统发生的，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开的，这使得研究谱系的特定成分成为可能。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出生的神经元产生的细胞和分子事件的序列。在小龙虾的大脑中，第一代前体（神经干细胞）不能自我更新，而是从其生态位外部来源补充。体外实验表明，造血系统是这些细胞的一个来源。本课题将：(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子对前体谱系的影响；(3)利用延时细胞跟踪技术实时探测血细胞与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对神经系统发育和进化机制的理解产生深远的影响。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，促进在进化背景下对造血和神经系统之间关系的重新审视，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.