SEMA3A Signaling Controls Layer-Specific Interneuron Branching in the Cerebellum

详细信息    查看全文

• 作者：Jean-Michel Cioni¹ ; ² ; ³ ; Ludovic Telley¹ ; ² ; ³ ; Vé ; ronique Saywell¹ ; ² ; ³ ; Christelle Cadilhac¹ ; ² ; ³ ; Carole Jourdan¹ ; ² ; ³ ; Andrea B. Huber⁴ ; Josh Z. Huang⁵ ; Cé ; line Jahannault-Talignani¹ ; ² ; ³ ; Fabrice Ango¹ ; ² ; ³ ; ^{fabrice.ango@igf.cnrs.fr}
• 刊名：Current Biology
• 出版年：2013
• 出版时间：20 May, 2013
• 年：2013
• 卷：23
• 期：10
• 页码：850-861
• 全文大小：2380 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

Background

GABAergic interneurons regulate the balance and dynamics of neural circuits, in part, by elaborating their strategically placed axon branches that innervate specific cellular and subcellular targets. However, the molecular mechanisms that regulate target-directed GABAergic axon branching are not well understood.

Results

Here we show that the secreted axon guidance molecule, SEMA3A, expressed locally by Purkinje cells, regulates cerebellar basket cell axon branching through its cognate receptor Neuropilin-1 (NRP1). SEMA3A was specifically localized and enriched in the Purkinje cell layer (PCL). In sema3A^?/? and nrp1^sema?/sema? mice lacking SEMA3A-binding domains, basket axon branching in PCL was reduced. We demonstrate that SEMA3A-induced axon branching was dependent on local recruitment of soluble guanylyl cyclase (sGC) to the plasma membrane of basket cells, and sGC subcellular trafficking was regulated by the Src kinase FYN. In fyn-deficient mice, basket axon terminal branching was reduced in PCL, but not in the molecular layer.

Conclusions

These results demonstrate a critical role of local SEMA3A signaling in layer-specific axonal branching, which contributes to target innervation.