Investigation of the cellular and molecular mediators of adult neurogenesis

再生通常被称为科学和医学研究中的“圣杯”，在中枢神经系统（CNS）中确实是一项迷人的壮举。事实上，在完全发育和高度集成的电路中，成年神经元的成功替换或再生是一种仅发生在特定脊椎动物物种中的现象。例如，哺乳动物通常不能进行成体再生，只能在大脑中的几个有限区域进行神经发生（新神经元的诞生）。相反，成年斑马鱼在中枢神经系统损伤后在整个大脑和脊髓中进行有力的再生过程，并在其一生中保持许多神经原性区域。在这个物种中负责神经发生和再生的分子因素，以及是什么使它们与哺乳动物不同，在很大程度上是未知的。确定必要的神经因子将提供必要的洞察力的分子机制，指导神经发生在成年脊椎动物和阐明自然的“再生器”和“非再生器”之间的进化差异。 我们目前对成人神经发生的认识是零散的，主要来自对哺乳动物大脑内少数神经发生部位的研究。此外，很少有人知道的基本细胞间的关系，主要是成人神经发生，特别是那些胶质细胞亚型之间，受损或新的神经元。因此，斑马鱼脊髓神经发生的特征，强调神经胶质细胞的生理和信号，将作出新的和重要的贡献，这一领域。我们的短期目标将致力于解决以下基本问题：什么样的分子因素控制斑马鱼脊髓的再生;胶质细胞在这个系统中发挥什么样的稳态或神经保护作用;最后，与损伤相关的炎症信号是否为再生奠定了基础？在这里，我们专注于嘌呤能信号家族，最普遍和进化保守的信号蛋白家族在中枢神经系统中，但也是最未知的。我们还旨在与哺乳动物微环境进行直接比较，以深入了解阻止该物种再生的细胞和分子成分。这些研究为随后的长期目标提供了重要的前奏，这些目标旨在识别负责调节神经生长，发育和神经可塑性的信号的适当编排。解开驱动斑马鱼这些过程的细胞和分子整合将是理解神经系统再生进化多样性的宝贵一步。

Regeneration is often referred to as the 'holy grail' in scientific and medical research and is truly a fascinating feat in the central nervous system (CNS). Indeed, the successful replacement or regrowth of adult neurons in fully developed and highly integrated circuits is a phenomenon that occurs in only select vertebrate species. Mammals, for example, are generally incapable of adult regeneration and undergo neurogenesis (the birth of new neurons) in only a few restricted regions within the brain. In contrast, adult zebrafish undertake a vigorous regenerative process throughout the brain and spinal cord following CNS injury and maintain many neurogenic regions throughout their lifetime. The molecular factors responsible for neurogenesis and regeneration in this species, and what makes them unique from mammals, are largely unknown. The identification of essential neurogenic factors will provide needed insight into the molecular mechanisms that instruct neurogenesis in adult vertebrates and shed light on the evolutionary differences between natural `regenerators' and `non-regenerators'. Our current knowledge of adult neurogenesis is fragmented and largely derived from studies of the few neurogenic sites within the mammalian brain. In addition, very little is known about the essential intercellular relationships that largely govern adult neurogenesis, particularly those between subtypes of glial cells, and damaged or new neurons. Characterization of neurogenesis in the zebrafish spinal cord, with an emphasis on glial physiology and signaling, will therefore make a novel and important contribution to this field. Our short-term goals will work to address the following fundamental questions: what molecular factors govern regeneration in the zebrafish spinal cord; what homeostatic or neuroprotective roles to glial cells play in this system; and finally, do inflammatory signals associated with injury set the stage for regeneration? Here, we focus on the purinergic signaling family, the most ubiquitous and evolutionarily conserved family of signaling proteins in the CNS, but also the most unknown. We also aim to make direct comparisons to the mammalian microenvironment to gain insight into both the cellular and molecular components that prevent regeneration in this species. These studies offer an important prelude to subsequent, long-term goals aimed at discerning the appropriate choreography of signals that are responsible for regulating neural growth, development and neuroplasticity. Unraveling the cellular and molecular integration that drives these processes in zebrafish will be an invaluable step in understanding the evolutionary diversity of nervous system regeneration.