期刊
DEVELOPMENT
卷 149, 期 23, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.201214
关键词
N-WASP; Arp2; 3; Actin; Purkinje cell; Dendrite; Maturation; Mouse
资金
- Japan Society for the Promotion of Science KAKENHI [21K20692, 20H03352]
- Takeda Science Foundation
- Naito Foundation
- NOVARTIS Foundation
- Kawano Masanori Memorial Public Interest Incorporated Foundation
- Life Science Foundation of Japan
This study demonstrates the crucial role of N-WASP-Arp2/3 signaling in the maturation of cerebellar Purkinje cell (PC) dendrites in vivo in mice, with proper activation of the signaling pathway being essential for the multiple steps of PC dendrite maturation.
During neural development, the actin filament network must be precisely regulated to form elaborate neurite structures. N-WASP tightly controls actin polymerization dynamics by activating an actin nucleator Arp2/3. However, the importance of N-WASP-Arp2/3 signaling in the assembly of neurite architecture in vivo has not been clarified. Here, we demonstrate that N-WASP-Arp2/3 signaling plays a crucial role in the maturation of cerebellar Purkinje cell (PC) dendrites in vivo in mice. N-WASP was expressed and activated in developing PCs. Inhibition of Arp2/3 and N-WASP from the beginning of dendrite formation severely disrupted the establishment of a single stem dendrite, which is a characteristic basic structure of PC dendrites. Inhibition of Arp2/3 after stem dendrite formation resulted in hypoplasia of the PC dendritic tree. Cdc42, an upstream activator of N-WASP, is required for N-WASP-Arp2/3 signaling-mediated PC dendrite maturation. In addition, overactivation of N-WASP is also detrimental to dendrite formation in PCs. These findings reveal that proper activation of N-WASP-Arp2/3 signaling is crucial for multiple steps of PC dendrite maturation in vivo.
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