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The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination.

Lu X, Hu X, Song L, An L, Duan M, Chen S, Zhao S - BMB Rep (2015)

Bottom Line: Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination.A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching.Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

ABSTRACT
Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

Show MeSH
Expression of FynR176A mutant induced the branching of cortical neurons. The brains were transfected with GFP or FynR176A at E15.5 and analyzed at E18.5. (A, A’) Normal morphology of migratory neurons in the GFP control group. (B, B’) Branching of cortical neurons in the FynR176A group. (C) Ratio of neurons with branches in the FynR176A mutant group compared with the GFP control group. Bars represent means ± standard deviation (*P < 0.05). (A, B) Scale bar = 100 μm, (A’ and B’) Scale bar = 10 μm.
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Figure 003: Expression of FynR176A mutant induced the branching of cortical neurons. The brains were transfected with GFP or FynR176A at E15.5 and analyzed at E18.5. (A, A’) Normal morphology of migratory neurons in the GFP control group. (B, B’) Branching of cortical neurons in the FynR176A group. (C) Ratio of neurons with branches in the FynR176A mutant group compared with the GFP control group. Bars represent means ± standard deviation (*P < 0.05). (A, B) Scale bar = 100 μm, (A’ and B’) Scale bar = 10 μm.

Mentions: As a member of the non-receptor tyrosine kinases, Fyn plays an essential role in actin cytoskeletal organization and cell migration (18-20). The results above show that overexpression of FynR176A arrested neuronal migration. We hypothesized that Fyn impaired neuronal migration by controlling actin cytoskeleton dynamics and neuronal morphogenesis. To assess this, we examined the morphology of the migrating neurons in the CP. Compared with the GFP control group, striking morphological changes occurred in the neurons transfected with FynR176A. As shown in Fig. 3 the transfected migrating neurons extended many branches and some of them lost the ‘classical’ neuronal morphology. The ratio of neurons having branches in the FynR176A expression group reached 19.67 ± 3.47%, while the GFP control group showed 6.13 ± 3.08%. Thus, our findings demonstrated that FynR176A impaired neuronal migration by controlling neuronal morphogenesis.


The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination.

Lu X, Hu X, Song L, An L, Duan M, Chen S, Zhao S - BMB Rep (2015)

Expression of FynR176A mutant induced the branching of cortical neurons. The brains were transfected with GFP or FynR176A at E15.5 and analyzed at E18.5. (A, A’) Normal morphology of migratory neurons in the GFP control group. (B, B’) Branching of cortical neurons in the FynR176A group. (C) Ratio of neurons with branches in the FynR176A mutant group compared with the GFP control group. Bars represent means ± standard deviation (*P < 0.05). (A, B) Scale bar = 100 μm, (A’ and B’) Scale bar = 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4352619&req=5

Figure 003: Expression of FynR176A mutant induced the branching of cortical neurons. The brains were transfected with GFP or FynR176A at E15.5 and analyzed at E18.5. (A, A’) Normal morphology of migratory neurons in the GFP control group. (B, B’) Branching of cortical neurons in the FynR176A group. (C) Ratio of neurons with branches in the FynR176A mutant group compared with the GFP control group. Bars represent means ± standard deviation (*P < 0.05). (A, B) Scale bar = 100 μm, (A’ and B’) Scale bar = 10 μm.
Mentions: As a member of the non-receptor tyrosine kinases, Fyn plays an essential role in actin cytoskeletal organization and cell migration (18-20). The results above show that overexpression of FynR176A arrested neuronal migration. We hypothesized that Fyn impaired neuronal migration by controlling actin cytoskeleton dynamics and neuronal morphogenesis. To assess this, we examined the morphology of the migrating neurons in the CP. Compared with the GFP control group, striking morphological changes occurred in the neurons transfected with FynR176A. As shown in Fig. 3 the transfected migrating neurons extended many branches and some of them lost the ‘classical’ neuronal morphology. The ratio of neurons having branches in the FynR176A expression group reached 19.67 ± 3.47%, while the GFP control group showed 6.13 ± 3.08%. Thus, our findings demonstrated that FynR176A impaired neuronal migration by controlling neuronal morphogenesis.

Bottom Line: Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination.A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching.Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

ABSTRACT
Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

Show MeSH