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The Journal of Neuroscience, June 1, 2003, 23(11):4613-4624
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Cell-Autonomous Mechanisms and Myelin-Associated Factors Contribute to the Development of Purkinje Axon Intracortical Plexus in the Rat Cerebellum
Sara Gianola,1
Tiziana Savio,2
Martin E. Schwab,3 and
Ferdinando Rossi1
1 Department of Neuroscience, Rita Levi Montalcini Centre for Brain Repair,
University of Turin, I-10125 Turin, Italy,
2 Department of Experimental Medicine, University of Genoa, I-16132 Genoa,
Italy, and
3 Swiss Federal Institute of Technology, Brain Research Institute, University of
Zurich, CH-8057 Zurich, Switzerland
The highly specific connection patterns of the mature CNS are shaped
through finely regulated processes of axon growth and retraction. To
investigate the relative contribution of cell-autonomous mechanisms and
extrinsic cues in these events, we examined the development of Purkinje axon
intracortical plexus in the rat cerebellum. During the first postnatal week,
several new processes sprout from focal swellings along the initial portion of
the Purkinje neurite and spread in the granular layer. Intense structural
plasticity occurs during the following week, with pruning of collateral
branches and remodeling of terminal arbors. The mature distribution of the
Purkinje infraganglionic plexus, confined within the most superficial portion
of the granular layer, is attained at approximately postnatal day 15. A
similar neuritic branching pattern is also developed by Purkinje cells grown
in cultures of dissociated cerebellar cells or transplanted to extracerebellar
CNS regions, suggesting that cell-autonomous mechanisms contribute to
determining the Purkinje axon phenotype.
The structural remodeling of Purkinje intracortical plexus is concomitant
with the development of cerebellar myelin. To ask whether myelin-associated
factors contribute to the morphological maturation of Purkinje neurites, we
prevented normal myelinogenesis by killing oligodendrocyte precursors with
5'-azacytidine or by applying neutralizing antibodies against the
myelin-associated neurite growth inhibitor Nogo-A. In both conditions,
Purkinje axons retained exuberant branches, and the terminal plexus spanned
the entire extent of the granular layer. Thus, the formation of Purkinje axon
collaterals is, in part, controlled by intrinsic determinants, but their
growth and distribution are regulated by environmental signals, among which
are myelin-derived cues.
Key words: Nogo; myelin-associated neurite growth inhibitory proteins; axonal plasticity; sprouting; pruning; neuritic branching; synaptogenesis; myelinogenesis; axon growth
Received Nov. 25, 2002;
revised Feb. 21, 2003;
accepted Mar. 24, 2003.
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