PLoS Biology (Feb 2011)

Development of axon-target specificity of ponto-cerebellar afferents.

  • Anna Kalinovsky,
  • Fatiha Boukhtouche,
  • Richard Blazeski,
  • Caroline Bornmann,
  • Noboru Suzuki,
  • Carol A Mason,
  • Peter Scheiffele

DOI
https://doi.org/10.1371/journal.pbio.1001013
Journal volume & issue
Vol. 9, no. 2
p. e1001013

Abstract

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The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber-Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber-Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development.