Project: Research project

Project Details


How do precise connections develop between neurons and targets?
Experimental and descriptive studies of a simple vertebrate system,
the development of muscle innervation in the chick embryo, have
shown that selective pathfinding by the growing of individual
neurites (the "growth cones") plays an essential role in the
genesis of the precise and orderly connections that are required
for the nervous system of function. As yet, little is known about
the cellular and molecular mechanisms of growth cone guidance. The
proposed studies contribute to the resolution of this major
unsolved problem in neurobiology.

The central aim of the proposed studies is to analyze the temporal
and spatial distribution of navigational cues and to characterize
guidance at the level of individual growth cones. Specific neural
populations are labeled with a non-toxin fluorescent dye that
allows visualization of active growth cones with image enhancement
technology. The central studies analyze the interactions of
individual growth cones with navigational cutes as they grow within
living sections of the chick embryo in culture. This culture
paradigm largely preserves the embryonic environment and yet allows
analysis of growth cone navigation with a greater degree of spatial
and temporal resolution than has heretofore been possible.

Studies in the first specific aim address the navigation of epaxial
motoneurons. These motoneurons are known to require a long-
distance cue from the epaxial muscles in order to grow out. The
proposed studies will characterize how growth cones respond to the
cue, determine the spatial-temporal distribution, source and
effective lifetime of the cue, show if the somata are essential
for growth cones to respond to the cue elucidate changes in the
internal structure of active growth cones and show how axons choose
one among two possible epaxial muscle targets. Studies in the
second specific aim address three tissues that border axon pathways
and appear to channel axon outgrowth by acting as barriers to axon
advancement. The proposed studies will chart the temporal-spatial
development of the barrier function, probe for molecules that
define this function and determine the cellular mechanism of
guidance. The third specific aim is to obtain monoconal antibodies
to the target-derived epaxial cue, the barrier tissues or to
subpopulations of motoneurons. The studies proposed are likely to
provide provocative information on the cellular and molecular
nature of axonal guidance cues.

Analysis of the cellular and molecular mechanisms that are
effective is specific neuronal pathfinding in the chick should give
insights into normal and abnormal development of the human nervous
system. Factors important to the development of the complexly
interdependent neuromuscular system may eventually be manipulated
to treat deficiencies in nerve-muscle interactions that are
responsible for human disease states. Finally, and understanding
of the processes conferring specificity on developing embryonic
connections is relevant to an understanding and proper treatment
of the relatively poor specific nerve regeneration in humans.
Effective start/end date1/1/9012/31/90


  • National Institute of Neurological Disorders and Stroke


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