DEVELOPMENT OF NEURONAL SPECIFICITY

  • Tosney, Kathryn (PI)

Project: Research project

Project Details

Description

DESCRIPTION (Investigator's Abstract): Growth cones, the growing tips
of axons, are considered the pathfinding organ of the neuron. They
sense many guidance cues by direct filopodial contact, but it has been
unclear how the contact actually directs growth cones. This proposal
focuses on a surprisingly specific aspect of contact-mediated guidance
that was detected using time-lapse microscopy in dissociated cell
culture. Growth cones of sensory neurons respond specifically to
contact with three populations that they normally encounter in the avian
embryo. Filopodial contact specifically alters the motile activity of
the growth cone itself. 1) Contact with posterior sclerotome locally
inhibits extension of veils. 2) Contact with Schwann cells locally
stimulates protrusion of large veils and increases veil stability. 3)
Contact with anterior sclerotome increases protrusion of both filopodia
and veils throughout the growth cone and then locally stimulates
preferential consolidation. These physiologically relevant responses are
sufficient to bias the direction of travel and to mediate behaviors such
as avoidance, but are more invariant than the gross behavior. They thus
appear to be the component that is most relevant to pathfinding. The
specificity of the responses strongly argues for specificity at the
molecular level. On contact, specific ligand-receptor binding is likely
to modulate distinguishable second messenger systems that cause specific
alterations in cytoskeletal dynamics. To investigate each of these
elements in turn, these invariant responses will be used as assays. Aim
1 characterizes cell surface molecular activities essential for two of
the responses by testing candidates implicated in pilot studies. Aim 2
assesses the role of calcium and other second messenger candidates in
each of the three responses. Aim 3 characterizes cytoskeletal changes
on contact with each population Interactions will be optically recorded,
with or without treatments with exogenous chemicals, and characterized
in detail. This work will elucidate mechanisms that control axonal
pathfinding, a process fundamental to human neural development.
StatusFinished
Effective start/end date12/31/8911/30/01

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.