Src family kinases are required for limb trajectory selection by spinal motor axons

Tzu Jen Kao, Elena Palmesino, Artur Kania

研究成果: 雜誌貢獻文章

30 引文 (Scopus)

摘要

Signal relay by guidance receptors at the axonal growth cone is a process essential for the assembly of a functional nervous system. We investigated the in vivo function of Src family kinases (SFKs) as growth cone guidance signaling intermediates in the context of spinal lateral motor column (LMC) motor axon projection toward the ventral or dorsal limb mesenchyme. Using in situ mRNA detection we determined that Src and Fyn are expressed in LMC motor neurons of chick and mouse embryos at the time of limb trajectory selection. Inhibition of SFK activity by C-terminal Src kinase (Csk) overexpression in chick LMC axons using in ovo electroporation resulted in LMC axons selecting the inappropriate dorsoventral trajectory within the limb mesenchyme, with medial LMC axon projecting into the dorsal and ventral limb nerve with apparently random incidence. We also detected LMC axon trajectory choice errors in Src mutant mice demonstrating a nonredundant role for Src in motor axon guidance in agreement with gain and loss of Src function in chick LMC neurons which led to the redirection of LMC axons. Finally, Csk-mediated SFK inhibition attenuated the retargeting of LMC axons caused by EphA or EphB over-expression, implying the participation of SFKs in Eph-mediated LMC motor axon guidance. In summary, our findings demonstrate that SFKs are essential for motor axon guidance and suggest that they play an important role in relaying ephrin:Eph signals that mediate the selection of motor axon trajectory in the limb.
原文英語
頁(從 - 到)5690-5700
頁數11
期刊Journal of Neuroscience
29
發行號17
DOIs
出版狀態已發佈 - 四月 29 2009
對外發佈Yes

指紋

src-Family Kinases
Axons
Extremities
Growth Cones
Motor Neurons
Mesoderm
Ephrins
Electroporation
Chick Embryo
Nervous System
Messenger RNA
Incidence

ASJC Scopus subject areas

  • Neuroscience(all)

引用此文

Src family kinases are required for limb trajectory selection by spinal motor axons. / Kao, Tzu Jen; Palmesino, Elena; Kania, Artur.

於: Journal of Neuroscience, 卷 29, 編號 17, 29.04.2009, p. 5690-5700.

研究成果: 雜誌貢獻文章

Kao, Tzu Jen ; Palmesino, Elena ; Kania, Artur. / Src family kinases are required for limb trajectory selection by spinal motor axons. 於: Journal of Neuroscience. 2009 ; 卷 29, 編號 17. 頁 5690-5700.
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