Environmental control of neural crest cell migration and proliferation

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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 eyeskin 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 behavioursObjective #2: Identify the molecular signals that participateObjective #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 productionAnticipated 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.