Development of axon-target specificity of ponto-cerebellar afferents

PLoS Biol. 2011 Feb 8;9(2):e1001013. doi: 10.1371/journal.pbio.1001013.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Axons / ultrastructure
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism
  • Bone Morphogenetic Protein 4 / physiology
  • Cell Communication / physiology*
  • Cerebellum / embryology
  • Cerebellum / physiology
  • Cerebellum / ultrastructure
  • Mice
  • Nerve Net / embryology
  • Nerve Net / physiology*
  • Purkinje Cells / physiology
  • Purkinje Cells / ultrastructure
  • Synaptic Transmission / physiology

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4