Abstract
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 invivo 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.
| Original language | English |
|---|---|
| Pages (from-to) | 311-323 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 Oct 9 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Cadherin-7 regulates mossy fiber connectivity in the cerebellum. / Kuwako, Ken ichiro; Nishimoto, Yoshinori; Kawase, Satoshi; Okano, Hirotaka James; Okano, Hideyuki.
In: Cell Reports, Vol. 9, No. 1, 09.10.2014, p. 311-323.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cadherin-7 regulates mossy fiber connectivity in the cerebellum
AU - Kuwako, Ken ichiro
AU - Nishimoto, Yoshinori
AU - Kawase, Satoshi
AU - Okano, Hirotaka James
AU - Okano, Hideyuki
PY - 2014/10/9
Y1 - 2014/10/9
N2 - 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 invivo 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.
AB - 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 invivo 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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U2 - 10.1016/j.celrep.2014.08.063
DO - 10.1016/j.celrep.2014.08.063
M3 - Article
C2 - 25284782
AN - SCOPUS:84907985796
VL - 9
SP - 311
EP - 323
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 1
ER -