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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.

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Related in: MedlinePlus

FynR176A mutant impairs neuronal migration. (A) Coronal sections of P1 brains that had been transfected with GFP plasmid and FynR176A mutant plasmid at E15.5. The GFP-positive cells showed the transfected cells; many neurons were arrested in the low-CP and IZ in the FynR176A group. (B) the ratio of neurons in PCZ to CP of the two groups (FynR176A group compared with GFP control group using the t-test. *P < 0.05). (C) Average fluorescent intensity in each layer was analyzed. Neurons in IZ showed significantly stronger fluorescent intensity (***P < 0.001). Bars indicate mean ± SEM. (A) Scale bar = 100 μm.
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Figure 001: FynR176A mutant impairs neuronal migration. (A) Coronal sections of P1 brains that had been transfected with GFP plasmid and FynR176A mutant plasmid at E15.5. The GFP-positive cells showed the transfected cells; many neurons were arrested in the low-CP and IZ in the FynR176A group. (B) the ratio of neurons in PCZ to CP of the two groups (FynR176A group compared with GFP control group using the t-test. *P < 0.05). (C) Average fluorescent intensity in each layer was analyzed. Neurons in IZ showed significantly stronger fluorescent intensity (***P < 0.001). Bars indicate mean ± SEM. (A) Scale bar = 100 μm.

Mentions: Several studies have reported that Fyn is required for neuronal migration (8-10, 17). We hypothesized that the SH2 domain of Fyn might play an important role in cortical neuronal migration. To examine this, we transfected the FynR176A plasmid into the newly generated neurons in the neocortex at E15.5 and analyzed 5 days later (at P1), while the pCAG-MCS-GFP plasmid was used as a control. As expected, many transfected cells were mislocated beneath the primitive cortical zone (PCZ), while most of them were located in the PCZ in the control group (Fig. 1). In the FynR176A -transfected group, many neurons were in the CP and IZ, where very few GFP-positive neurons were found in the control group. Statistical analysis showed that the ratio of neurons in PCZ to CP was significantly different between the two groups. These findings suggested that point mutation of the Fyn SH2 domain impaired migration and the final location of the cortical neurons.


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)

FynR176A mutant impairs neuronal migration. (A) Coronal sections of P1 brains that had been transfected with GFP plasmid and FynR176A mutant plasmid at E15.5. The GFP-positive cells showed the transfected cells; many neurons were arrested in the low-CP and IZ in the FynR176A group. (B) the ratio of neurons in PCZ to CP of the two groups (FynR176A group compared with GFP control group using the t-test. *P < 0.05). (C) Average fluorescent intensity in each layer was analyzed. Neurons in IZ showed significantly stronger fluorescent intensity (***P < 0.001). Bars indicate mean ± SEM. (A) Scale bar = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 001: FynR176A mutant impairs neuronal migration. (A) Coronal sections of P1 brains that had been transfected with GFP plasmid and FynR176A mutant plasmid at E15.5. The GFP-positive cells showed the transfected cells; many neurons were arrested in the low-CP and IZ in the FynR176A group. (B) the ratio of neurons in PCZ to CP of the two groups (FynR176A group compared with GFP control group using the t-test. *P < 0.05). (C) Average fluorescent intensity in each layer was analyzed. Neurons in IZ showed significantly stronger fluorescent intensity (***P < 0.001). Bars indicate mean ± SEM. (A) Scale bar = 100 μm.
Mentions: Several studies have reported that Fyn is required for neuronal migration (8-10, 17). We hypothesized that the SH2 domain of Fyn might play an important role in cortical neuronal migration. To examine this, we transfected the FynR176A plasmid into the newly generated neurons in the neocortex at E15.5 and analyzed 5 days later (at P1), while the pCAG-MCS-GFP plasmid was used as a control. As expected, many transfected cells were mislocated beneath the primitive cortical zone (PCZ), while most of them were located in the PCZ in the control group (Fig. 1). In the FynR176A -transfected group, many neurons were in the CP and IZ, where very few GFP-positive neurons were found in the control group. Statistical analysis showed that the ratio of neurons in PCZ to CP was significantly different between the two groups. These findings suggested that point mutation of the Fyn SH2 domain impaired migration and the final location of the cortical neurons.

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
Related in: MedlinePlus