Environmental control of neural crest cell migration and proliferation

外周神经系统对机体对内外环境变化的反应起着至关重要的作用。周围神经系统的大部分细胞——包括色素细胞、神经元和胶质细胞——都来源于神经嵴细胞（NCC）。NCCs是在形成的大脑和脊髓边缘作为未分化的增殖细胞产生的，这些细胞从大脑移动到周围的特定靶组织，并成熟为特定的细胞类型。我们只了解这个迷人过程的一些步骤。一个重要的知识缺口，也是本提案的重点，是生物体的环境如何影响NCC特定细胞类型的产生。******我们研究皮肤的色素细胞（黑素细胞），因为我们发现环境光通过特定的神经回路控制黑素细胞的数量，该神经回路影响NCC祖细胞的黑素细胞产生。这个回路在生物学上是重要的，因为通过控制色素细胞的数量，生物体可以伪装和保护紫外线。我们使用青蛙和鱼类胚胎模型的组合，为了解大脑如何调节NCC祖细胞和动物皮肤颜色提供了绝佳的机会：1)系统的输入（光/暗）可以在时间和空间上控制，2)回路的输出只需要计算皮肤黑色素细胞，3)从眼睛到皮肤的整个回路都可以用于实验。定义光（环境）的细胞和分子成分⇒NCC（大脑）⇒色素细胞（外围）电路是我们研究项目的目标。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分泌控制NCC生物学和皮肤颜色的因素的假设：******目标#1：定义神经回路和依赖光的NCC和黑素细胞行为***目标#2：确定参与的分子信号***目标#3：使用遗传模型实时定义NCCs/黑素细胞在体内的行为，以及黑素细胞产生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，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，将为了解大脑如何响应感觉输入来动态调节周围神经来源的细胞提供重要的见解。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，以及关键的数据分析和沟通技巧，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。

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.