The Journal of Neuroscience, March 15, 2003, 23(6):2294
N-Cadherin Regulates Ingrowth and Laminar Targeting of
Thalamocortical Axons
Kira
Poskanzer,
Leigh A.
Needleman,
Ozlem
Bozdagi, and
George W.
Huntley
Fishberg Research Center for Neurobiology, The Mount Sinai School
of Medicine, New York, New York 10029
Thalamocortical axons are precisely targeted to cortical layer IV,
but the identity of specific molecules that govern the establishment of
laminar specificity in the thalamocortical projection has been elusive.
In this study, we test the role of
N-cadherin, a homophilic cell adhesion
molecule, in laminar targeting of thalamocortical axons using
cocultured thalamic and cortical slice explants exposed to
N-cadherin function-blocking antibodies
or inhibitory peptides. In untreated cocultures, labeled
thalamocortical axons normally grow to and stop in layer IV, forming
terminal-like arbors. In the
N-cadherin-blocked cocultures, thalamic
axons reach layer IV by growing through deep layers at the same rate as
those in the untreated cocultures, but instead of terminating in layer IV, they continue growing uninterruptedly through layer IV and extend
into supragranular layers to reach the outermost cortical edge, where
some form terminal-like arbors in this aberrant laminar position. In
cocultures in which the cortical slice is taken at an earlier
maturational stage, one that corresponds to a time when thalamic axons
are normally growing through deep layers before the emergence of layer
IV from the cortical plate, thalamic axon ingrowth through deep layers
is significantly attenuated by N-cadherin blocking reagents. These data indicate that
N-cadherin has multifaceted roles in
establishing the thalamocortical projection, governing aspects of both
thalamic axon ingrowth and laminar targeting by acting as a layer IV
stop signal, which progressively change in parallel with the
maturational state of the cortex.
Key words:
synaptogenesis; axon outgrowth; cell adhesion
molecules; stop signal; axon targeting; ventrobasal nucleus; barrel
cortex; thalamocortical
Copyright © 2003 Society for Neuroscience 0270-6474/03/2362294-12$05.00/0
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