Development of Axon-Target Specificity of Ponto-Cerebellar Afferents
| Autor: | Carol A. Mason, Noboru Suzuki, Anna Kalinovsky, Peter Scheiffele, Fatiha Boukhtouche, Richard Blazeski, Caroline Bornmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cell signaling
Cerebellum Neural Networks Nerve net QH301-705.5 Bone Morphogenetic Protein 4 Cell Communication Neurotransmission Biology Signaling Pathways Synaptic Transmission General Biochemistry Genetics and Molecular Biology Synapse 03 medical and health sciences Mice Purkinje Cells 0302 clinical medicine medicine Animals Axon Biology (General) 030304 developmental biology 0303 health sciences General Immunology and Microbiology Neuronal Morphology General Neuroscience Anatomy Axons Neuroanatomy medicine.anatomical_structure Bone morphogenetic protein 4 Synaptic specificity Cellular Neuroscience Molecular Neuroscience Nerve Net General Agricultural and Biological Sciences Neuroscience 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS Biology PLOS BIOLOGY PLoS Biology, Vol 9, Iss 2, p e1001013 (2011) PLoS biology |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | 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. Author Summary Brain functions rely on highly selective neuronal networks which are assembled during development. Network assembly involves targeted neuronal growth followed by recognition of the appropriate target cells and selective synapse formation. How neuronal processes select their appropriate target cells from an array of interaction partners is poorly understood. In this study, we have addressed this question for the axons emerging from the pontine gray nucleus, a major brainstem nucleus that relays information between the cortex and the cerebellum, a brain area responsible for the control of skilled movements but also emotional processing. Using advanced microscopy techniques, we find that developing mossy fibers establish synaptic contacts rather promiscuously, and elaborate extensive synapses with Purkinje cells, an inappropriate target. These contacts are subsequently eliminated, and proper synaptic connectivity is then restricted to granule and Golgi neurons. We identify bone morphogenetic protein 4 (BMP4) as a regulator of these inappropriate mossy fiber-Purkinje cell contacts. BMP growth factors are best known for their functions in cell specification during embryonic development, and our results support an additional retrograde signaling function between axons and their target cells in early postnatal stages. In summary, we show that the specificity of the synaptic connections in the ponto-cerebellar circuit emerges through extensive elimination of transient synapses. |
| Databáze: | OpenAIRE |
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