Journal
CELL REPORTS
Volume 9, Issue 1, Pages 311-323Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2014.08.063
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Funding
- Japan Society for the Promotion of Science
- Brain Science Foundation
- Kanae Foundation for the Promotion of Medical Science
- Narishige Neuroscience Research Foundation
- Funding Program for World-leading Innovative R&D on Science and Technology
- San Bio Co., Ltd.
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To establish highly precise patterns of neural connectivity, developing axons must stop growing at their appropriate destinations and specifically synapse with target cells. However, the molecular mechanisms governing these sequential steps remain poorly understood. Here, we demonstrate that cadherin-7 (Cdh7) plays a dual role in axonal growth termination and specific synapse formation during the development of the cerebellar mossy fiber circuit. Cdh7 is expressed in mossy fiber pontine nucleus (PN) neurons and their target cerebellar granule neurons during synaptogenesis and selectively mediates synapse formation between those neurons. Additionally, Cdh7 presented by mature granule neurons diminishes the growth potential of PN axons. Furthermore, knockdown of Cdh7 in PN neurons in vivo severely impairs the connectivity of PN axons in the developing cerebellum. These findings reveal a mechanism by which a single bifunctional cell-surface receptor orchestrates precise wiring by regulating axonal growth potential and synaptic specificity.
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