University of Louisville

Cytoskeletal Involvement in Ephrin-mediated Axon Guidance

Institution

University of Louisville

Abstract

Axon guidance is the mechanism by which a nerve cell extends a thin process, the axon, over potentially thousands of other cells to accurately make a connection (synapse) with a target cell. This process is led by the growth cone, a motile receptor-rich structure at the end of growing axons that samples its surroundings to determine direction of growth. The extracellular matrix protein laminin, and the cell adhesion molecule n-cadherin, both promote axonal extension. The growth factor, BDNF, can also act as an attractive factor, although its primary function is to promote survival. In contrast, the ephrins are repulsive guidance molecules that cause the growth cone to collapse within 30 minutes. This collapse “resets” the growth cone and it starts moving in another direction. Cytoskeletal effectors are involved in the collapse, but the specific role of the cytoskeleton in this process is unknown. Recent data from our lab has shown that the ephrin-induced collapse can be modulated by BDNF and n-cadherin. This presents a model for the study of cytoskeletal contribution to the collapse. Retinal neurons are stained to reveal the actin cytoskeleton, and alterations to the cytoskeleton are correlated with the collapse of the growth cones after contact with ephrins, in the presence and absence of modulatory elements. The hypothesis predicts that cytoskeletal rearrangement and retraction significantly precedes and causes visible growth cone collapse.

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Cytoskeletal Involvement in Ephrin-mediated Axon Guidance

Axon guidance is the mechanism by which a nerve cell extends a thin process, the axon, over potentially thousands of other cells to accurately make a connection (synapse) with a target cell. This process is led by the growth cone, a motile receptor-rich structure at the end of growing axons that samples its surroundings to determine direction of growth. The extracellular matrix protein laminin, and the cell adhesion molecule n-cadherin, both promote axonal extension. The growth factor, BDNF, can also act as an attractive factor, although its primary function is to promote survival. In contrast, the ephrins are repulsive guidance molecules that cause the growth cone to collapse within 30 minutes. This collapse “resets” the growth cone and it starts moving in another direction. Cytoskeletal effectors are involved in the collapse, but the specific role of the cytoskeleton in this process is unknown. Recent data from our lab has shown that the ephrin-induced collapse can be modulated by BDNF and n-cadherin. This presents a model for the study of cytoskeletal contribution to the collapse. Retinal neurons are stained to reveal the actin cytoskeleton, and alterations to the cytoskeleton are correlated with the collapse of the growth cones after contact with ephrins, in the presence and absence of modulatory elements. The hypothesis predicts that cytoskeletal rearrangement and retraction significantly precedes and causes visible growth cone collapse.