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Axonal/Dendritic Growth and Circuit Formation

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Cadherin-7 regulates the circuit connectivity of the cerebellar mossy fiber

  • P2-101
  • 桑子 賢一郎 / Kenichiro Kuwako:1 岡野 栄之 / Hideyuki Okano:1 
  • 1:慶應大医学部生理学 / Department of Physiology, Keio University School of Medicine 

Precise synaptic connections in the nervous system are crucial for the assembly of functional neural circuits. To establish highly precise patterns of neural connectivity, developing axons must properly stop growing at their destinations and specifically synapse with target cells. Since axons must be essentially stabilized to develop synapses soon after they connect to their ultimate target cells, axon-target connection and axon growth termination should be finely orchestrated in a spatiotemporal manner. However, the molecular mechanisms governing these sequential steps remain poorly understood. Here, we demonstrate that cadherin-7 (Cdh7) plays a dual role in specific synaptic connection and axon growth termination during the formation of the cerebellar mossy fiber circuit. Cdh7 is expressed in mossy fiber neurons, including pontine nucleus (PN) neurons, and cerebellar neurons at the synaptogenic stage in mice. Cdh7 localizes in the axon terminals of PN neurons and the dendrites of cerebellar granule neurons that are the target cells of PN axons, whereas it is highly confined to the golgi apparatus, but not the cell-surface, in Purkinje cells. The homophilic interaction of Cdh7 induces presynaptic differentiation in PN axons. Furthermore, Cdh7 selectively mediates the synaptic connection of PN axons with granule neurons but not with Purkinje cells. Additionally, Cdh7 presented by surrounding cells inhibits the axon growth of PN neurons in a developmental stage-dependent manner, and mature granule neurons diminish the growth potential of PN axons through Cdh7. The shRNA-mediated knockdown of Cdh7 expression in developing PN neurons in vivo severely impairs the connectivity of PN axons in the developing cerebellum. These findings reveal a novel mechanism that a bifunctional single cell-surface receptor orchestrates precise wiring by regulating synaptic specificity and axon growth potential.

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