Environmental control of neural crest cell migration and proliferation

神经嵴细胞迁移和增殖的环境控制

• 批准号: RGPIN-2018-03909
• 负责人: McFarlane, Sarah
• 金额: $ 4.23万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=659250
• 关键词: Environmental; control; neural; crest; cell

The peripheral nervous system is critical for mounting and coordinating an organism's response to changes in its internal and external environment. Most cells of the peripheral nervous system -- including pigment cells, neurons and glia -- are derived from neural crest cells (NCC). NCCs are generated at the edge of the forming brain and spinal cord as undifferentiated, proliferative cells that locomote away from the brain to particular target tissues in the periphery, and mature into specific cell types. We understand only some of the steps of this fascinating process. An important knowledge gap, and the focus of this proposal, is how the organism's environment influences the production of specific cell types by NCC.******We study the pigmented cells (melanophores) of the skin, because we discovered that environmental light controls the number of melanophores via a specific neural circuit that affects melanophore production by NCC progenitors. This circuit is biologically important, as through the control of pigment cell numbers an organism is afforded camouflage and UV protection. We use a combination of frog and fish embryo models that provide outstanding opportunities to understand how the brain can adjust NCC progenitors and an animal's skin colour: 1) The input to the system (light/dark) can be temporally and spatially controlled, 2) The output of the circuit simply requires counting of skin melanophores, and 3) The entire circuit from eye⇒skin is accessible for experimentation. Defining the cellular and molecular components of the light (environment)⇒NCC (brain)⇒pigment cell (periphery) circuit is the goal of our research program. We will test the hypothesis that light perceived by the eye acts through a nerve circuit to secrete factors that control NCC biology and thus skin colour, by addressing the following objectives:******Objective #1: Define the nerve circuit and light-dependent NCC and melanophore behaviours***Objective #2: Identify the molecular signals that participate***Objective #3: Use genetic models to define the behaviour of NCCs/melanophores in vivo in real time, and short- and long-term neural regulation of melanophore production******Anticipated Benefits: Our research program is at the forefront of understanding how the external environment can directly impact the developing nervous system, in that we have identified a natural signal, light, that controls neural progenitor biology to adapt the organism to its environment. Understanding how this takes place will provide critical insights into how the brain responds to sensory input to dynamically regulate neurally-derived cells of the periphery. Importantly, our HQP will learn cutting-edge CRISPR gene editing technology, 4-D tracking of cells in vivo, drug screening methods, and critical data analytical and communication skills, which will position them well as academic and industry leaders in Canada's natural sciences sector.

周围神经系统对于组织和协调机体对内外环境变化的反应至关重要。周围神经系统的大多数细胞-包括色素细胞，神经元和神经胶质-都来自神经嵴细胞（NCC）。NCC作为未分化的增殖细胞在形成的脑和脊髓的边缘处产生，所述未分化的增殖细胞从脑迁移到外周中的特定靶组织，并成熟为特定的细胞类型。我们只了解这个迷人过程的一些步骤。一个重要的知识差距，也是本提案的重点，是生物体的环境如何影响NCC产生特定细胞类型。*我们研究皮肤的色素细胞（黑色素细胞），因为我们发现环境光通过一个特定的神经回路控制黑色素细胞的数量，该神经回路影响NCC祖细胞的黑色素细胞产生。这个回路在生物学上很重要，因为通过控制色素细胞数量，生物体可以获得伪装和紫外线保护。我们使用青蛙和鱼胚胎模型的组合，这些模型提供了很好的机会来了解大脑如何调节NCC祖细胞和动物的肤色：1）系统的输入（亮/暗）可以在时间和空间上进行控制，2）电路的输出只需要对皮肤黑色素细胞进行计数，3）来自眼睛皮肤的整个电路可用于实验。定义光（环境）-NCC（大脑）-色素细胞（外周）回路的细胞和分子组成部分是我们研究计划的目标。我们将通过解决以下目标来测试眼睛感知的光通过神经回路作用以分泌控制NCC生物学并因此控制肤色的因子的假设：** 目标#1：定义神经回路和光依赖性NCC和黑色素细胞行为 * 目标#2：识别参与的分子信号 * 目标#3：使用遗传模型来定义真实的体内NCC/黑色素细胞的行为，以及黑色素细胞产生的短期和长期神经调节 ** 预期益处：我们的研究项目处于了解外部环境如何直接影响发育中的神经系统的最前沿，因为我们已经确定了一种自然信号，光，控制神经祖细胞生物学使生物体适应环境。了解这是如何发生的将提供关键的见解，大脑如何响应感官输入，以动态调节外周神经源性细胞。重要的是，我们的HQP将学习尖端的CRISPR基因编辑技术，体内细胞的4-D跟踪，药物筛选方法以及关键数据分析和沟通技能，这将使他们成为加拿大自然科学领域的学术和行业领导者。