ROLES OF NEURAL INTEGRIN DURING AXON DEVELOPMENT

Project: Research project

Project Details

Description

DESCRIPTION (Verbatim from the Applicant's Abstract): This project investigates
the roles of integrin during axon navigation in vivo. A major challenge in
neuroscience today is to explain the genetic porgrams that direct development
of the brain. The brain is composed of multi-layered networks of neurons that
self-organize specific connections. How does a neuronal growth cone communicate
with other cells while choosing specific pathways? What molecules are there to
mediate such cell recognition and migration? The prevailing view is that
accurate axon guidance relies on the activation of cell surface receptors that
translate extrinsic cues into directed cytoskeletal rearrangement within a
growth cone. Integrin is a family of multi-functional cell surface
receptor/adhesion molecules, enriched in axonal growth cones. Although it has
been proposed to play unique and important roles during migration and network
formation of neurons, the main functions of integrin during axon navigation are
not well understood in vivo. Drosophila offers both genetic and cell biological
advantages. We apply our lab's expertise and examine the axon navigation
defects in integrin knock out mutants, determine the cell autonomous
requirement of integrin in axons and begin characterizing how integrin works
inside a growth cone in situ. Specific hypotheses will be evaluated in real
life contexts (in situ). Aim 1 evaluates both "speed controller" and "decision
mediator" models for integrin's roles during axon navigation. It also tests the
idea that much of axon defects in knock out mutants reflect integrin's "cell
autonomy" inside neurons that express integrin. Aim 2 looks inside axons and
begins to evaluate the idea that integrin works through forming "focal
adhesions" and/or "filopodia enrichment." It also examined the differences
between alphaPS1 and alphaPS2 knock out phenotypes and ask whether the
differences owe to their "expression-based distinctions" or "structure-based
distinctions." Whereas Aim 1 establishes cellular contexts in which Integrin's
in vivo roles can be studied during axon navigation, Aim 2 explores into the
molecule-level experimentation in the same in vivo contexts. Thus, the project
"bridges" the gap between the wealth of in vitro (molecule-level) knowledge and
the absence of in vivo (cell-level) analysis of integrin. Through this project,
we move from the question of "what is integrin capable of doing?" to that of
"what is integrin really doing" in real life contexts in situ.
StatusFinished
Effective start/end date6/1/005/31/05

Funding

  • National Institute of Neurological Disorders and Stroke: $46,252.00
  • National Institute of Neurological Disorders and Stroke: $220,014.00
  • National Institute of Neurological Disorders and Stroke: $220,290.00
  • National Institute of Neurological Disorders and Stroke: $270,558.00
  • National Institute of Neurological Disorders and Stroke: $267,183.00

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