@article{10.1371/journal.pbio.1001013, doi = {10.1371/journal.pbio.1001013}, author = {Kalinovsky, Anna AND Boukhtouche, Fatiha AND Blazeski, Richard AND Bornmann, Caroline AND Suzuki, Noboru AND Mason, Carol A. AND Scheiffele, Peter}, journal = {PLOS Biology}, publisher = {Public Library of Science}, title = {Development of Axon-Target Specificity of Ponto-Cerebellar Afferents}, year = {2011}, month = {02}, volume = {9}, url = {https://doi.org/10.1371/journal.pbio.1001013}, pages = {1-16}, 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.}, number = {2}, }