Environmental control of neural crest cell migration and proliferation

外周神经系统对于建立和协调生物体对其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、神经元和神经胶质细胞--都来自神经脊细胞(NCC)。NCC是在形成的脑和脊髓的边缘产生的，作为未分化的、增殖的细胞，从大脑移动到外围的特定靶组织，并成熟为特定的细胞类型。我们只了解这个令人着迷的过程的一些步骤。一个重要的知识缺口，也是这项建议的焦点，是有机体的环境如何影响NCC产生特定类型的细胞。*我们研究皮肤的色素细胞(黑素载体)，因为我们发现环境光通过影响NCC前体细胞黑素载体产生的特定神经回路控制黑素载体的数量。这个回路在生物学上很重要，因为通过控制色素细胞的数量，生物体被提供了伪装和紫外线保护。我们使用青蛙和鱼胚胎模型的组合，为了解大脑如何调整NCC祖细胞和动物的皮肤颜色提供了绝佳的机会：1)系统的输入(明/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素细胞进行计数，以及3)从眼睛⇒皮肤的整个电路可以进行实验。确定光(环境)⇒NCC(脑)⇒色素细胞(外周)电路的细胞和分子成分是我们研究计划的目标。我们将通过以下目标来测试这样的假设：眼睛感知的光通过神经回路分泌控制NCC生物学从而控制皮肤颜色的因子：*目标#1：定义神经回路和依赖光的NCC和黑素载体行为*目标#2：识别参与的分子信号*目标#3：使用遗传模型实时定义NCC/黑素载体在体内的行为，以及对黑素载体生产的短期和长期神经调节*预期好处：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前沿，因为我们已经确定了一种自然信号，光，它控制神经前体生物学使有机体适应其环境。了解这是如何发生的，将为大脑如何对感觉输入做出反应，以动态调节外周神经源性细胞提供关键的见解。重要的是，我们的HQP将学习尖端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先者。

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.