| First Author | Kalinovsky A | Year | 2011 |
| Journal | PLoS Biol | Volume | 9 |
| Issue | 2 | Pages | e1001013 |
| PubMed ID | 21346800 | Mgi Jnum | J:170711 |
| Mgi Id | MGI:4947173 | Doi | 10.1371/journal.pbio.1001013 |
| Citation | Kalinovsky A, et al. (2011) Development of axon-target specificity of ponto-cerebellar afferents. PLoS Biol 9(2):e1001013 |
| abstractText | 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. |
