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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-10-17
pubmed:abstractText
We review studies from our laboratory over the last 6 years that indicate the mechanical tension on the axons of cultured neurons is a regulator and stimulator of axonal elongation and retraction. Using calibrated glass needles to measure or apply tension, we have accumulated direct evidence for tension as a regulator of four different phases of axonal development: 1) axonal initiation; 2) growth cone-mediated elongation; 3) growth after the growth cone reaches its target; and 4) axonal retraction. Our results can be summarized by a model in which tension levels behave as a three position controller, like a double-pole, double-throw electric switch. The three settings of this switch are separated by tension thresholds: 1) Above the upper threshold, tension acts as a stimulator for axonal elongation and initiation. The growth rate of the neurite is directly proportional to the magnitude of tension on the neurite. Similar levels of tension can initiate neurites de novo from chick sensory neurons. These tension-induced axons are normal in their axial array of microtubules and in the development of a motile growth cone. Under normal conditions of growth, our evidence supports the notion that the growth cone stimulates axonal elongation by acting as a tractor, pulling on the neurite; 2) The "switch" also has a setting for axonal retraction, which occurs at tension magnitudes below some different, lower tension threshold. Our evidence indicates that such axonal retraction involves active force generation by the neurite shaft; and 3) Between the two thresholds, the switch is in a neutral position and the neurite behaves passively as a viscoelastic solid. That is, the neurite stretches in response to tension but there is no true growth, i.e. no microtubule assembly or membrane addition etc. Thus, it seems tension can be regarded as a kind of "second messenger" whose level regulates axonal development. The mechanism of action of developmental neurotoxicants may be to alter the production of, or the sensitivity to, tension. At the least, this evidence that mechanical force regulates axonal growth provides a new avenue of investigation into neurotoxic mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:issn
0161-813X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
95-107
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Mechanical tension as a regulator of axonal development.
pubmed:affiliation
Department of Physiology, Michigan State University, East Lansing 48824-1101.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Review