Molecular and Cellular Bioengineering Research Experiences for Undergraduates (REU) Program
Neuron Migration and Axonal Outgrowth: A Mechanotactic Event
P.I.: Aranda-Espinoza
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Two forms of migration are fundamental in the formation of the nervous system: neurite elongation and cell body migration. Understanding how neurons extend dendrites and axons, elongate at a particular rate, and stop growing is fundamental to comprehend the development of the nervous system. Surprisingly, the original neuron is a spherical object, from which axon(s) and dendrites sprout out, at the right time and in the right direction, to form the appropriate synaptic connections and hence brain function. To carry out this task the neurite has a highly sensitive structure, the growth cone. Motility of the growth cone is dictated by repelling or attractive extracellular cues. Sometimes, before the neuron establishes connections, it migrates the length of hundreds of cell bodies from its birthplace to its final destination where the axon and dendrites begin to extend. Disordered neuronal migration can lead to neurological conditions, such as periventricular heterotopia (PA) and lissencephaly. Even more, after trauma to the central nervous system, injured axons cannot regenerate due to growth of inhibitory molecules and physical barriers including the formation of a glial scar.
Little is known about the influences of the mechanical properties of the substrate on the motility of neurons and the outgrowth of their neurites, in particular the axon. Understanding of the substrate effects and further tailoring of the substrate to control neuron motility could have vast implications in the treatment of neurological conditions, such as regeneration of axons after trauma. The movement of the growth cone and/or the neuron over or through a substrate requires the combined and synchronized action of adhesion forces, traction stresses, membrane exchange (tension), and changes in cytoskeletal structure and dynamics. It is generally accepted that the key ingredient in all
of these processes is the actin cytoskeleton, while other proteins such as microtubules are just secondary players. For example, microtubules help to maintain the elongated neurite, but are not capable of generating the forces necessary for neurite or cell migration. In this project, students will measure the outgrowth of axons and migration of cell bodies on compliant substrates. Explore the molecular mechanisms that control such outgrowth and migration.
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