Neurogenesis in the adult Drosophila brain

项目摘要 人类治疗性神经再生的障碍之一是大多数神经干细胞的缺乏。 成人大脑的区域。尽管如此，诱导常驻细胞再生将是有利的。在……里面 此外，如果能够从驻留细胞中再生神经，该领域的进展将会加快 使用遗传模型生物体进行了研究。为此，我们开发了一种新的成人神经发生 果蝇中央大脑的模型。我们发现，尽管没有已知的神经 成年果蝇中央脑中的祖细胞在损伤后增殖，产生两个新的 神经元和新的神经胶质细胞。此外，新的神经元将轴突和树突投射到特定的靶点。 地区。我们还观察到行为缺陷的功能恢复，表明新的神经元整合 适当地进入神经回路。我们的结果是范式的转变，因为它们表明常驻大脑 细胞可以调节神经再生。在这里，我们建议利用该模型来研究信令 调节成人神经发生的途径和细胞机制。基于令人信服的初步数据， 我们的中心假设是，成年出生的神经元负责脑损伤后的功能恢复和 这些神经元是从成年出生的神经胶质细胞中分离出来的。这一假说得到了以下几行的支持 我们正在进行的工作中的证据。我们已经确定，并正在研究独特上调的基因 在神经再生过程中。这里提出的工作将提供关于分子机制的关键数据。 这是成人神经发生的基础。我们的工作是创新的，并具有翻译相关性，因为它改变了 神经再生的焦点从干细胞移植转向驻留细胞群体及其 可能导致确定刺激人类大脑再生的治疗靶点。

Project Summary One of the barriers to therapeutic neural regeneration in humans is the absence of neural stem cells in most regions of the adult brain. Nonetheless, it would be advantageous to induce regeneration from resident cells. In addition, progress in the field would be accelerated if neural regeneration from resident cells could be investigated using a genetic model organism. Toward this end, we have developed a novel adult neurogenesis model in the Drosophila melanogaster central brain. We find that despite the absence of known neural progenitors, cells in the adult Drosophila central brain proliferate following injury, giving rise to both new neurons and new glial cells. Further, the new neurons project both axons and dendrites to specific target regions. We also observe functional recovery of behavioral deficits, suggesting that the new neurons integrate appropriately into neural circuits. Our results are paradigm-shifting because they suggest that resident brain cells can mediate neural regeneration. Here, we propose to utilize the model to investigate the signaling pathways and cellular mechanisms that regulate adult neurogenesis. Based on compelling preliminary data, our central hypothesis is that adult-born neurons are responsible for functional recovery from brain injury and that these neurons arise separately from adult-born glia. This hypothesis is supported by multiple lines of evidence from our ongoing work. We have identified, and are now investigating, genes uniquely upregulated during neural regeneration. The work proposed here will provide critical data about the molecular mechanisms that underlie that adult neurogenesis. Our work is innovative and has translational relevance because it shifts the focus of neural regeneration away from stem cell transplants and toward resident cell populations and it may lead to the identification of therapeutic targets for the stimulation of brain regeneration in humans.