title: Development of axon-target specificity of ponto-cerebellar afferents.
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.
authors.affiliation: Department of Physiology & Cellular Biophysics and Department of Neuroscience, Columbia University, New York, New York, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Kalinovsky
authors.forename: Fatiha
authors.initials: F
authors.lastname: Boukhtouche
authors.forename: Richard
authors.initials: R
authors.lastname: Blazeski
authors.forename: Caroline
authors.initials: C
authors.lastname: Bornmann
authors.forename: Noboru
authors.initials: N
authors.lastname: Suzuki
authors.forename: Carol A
authors.initials: CA
authors.lastname: Mason
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002531:Cerebellum / Q000196:embryology / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D009415:Nerve Net / Q000196:embryology / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4