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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
Over-expression of FynR176A induced neuronal aggregation in the DCP and IZ. (A, B) Sections of P1 brain transfected with FynR176A at E15.5 showed many aggregations formed in the DCP and IZ. (A’, B’) Higher magnification of FynR176A positive neurons formed aggregations in the DCP and IZ. The arrow points to the GFP+/DAPI+/Brn2+ (red). (A, B) Scale bar = 100 μm, (A’) Scale bar = 20 μm, (B’) Scale bar = 10 μm.
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Figure 002: Over-expression of FynR176A induced neuronal aggregation in the DCP and IZ. (A, B) Sections of P1 brain transfected with FynR176A at E15.5 showed many aggregations formed in the DCP and IZ. (A’, B’) Higher magnification of FynR176A positive neurons formed aggregations in the DCP and IZ. The arrow points to the GFP+/DAPI+/Brn2+ (red). (A, B) Scale bar = 100 μm, (A’) Scale bar = 20 μm, (B’) Scale bar = 10 μm.

Mentions: Our study showed that overexpression of the SH2 domain mutant form of Fyn also induced neuronal aggregation in the CP and IZ of mouse cerebral cortex (Fig. 2). The upper layer neuronal marker ‘Brn2’ staining suggested that the aggregated neurons in the CP/IZ belonged to layer II/III. The aggregation zone was packed densely with cells and clearly demarcated from the surroundings. There was an average of six aggregations in every section. The average cell number in the aggregation zone was 18.6 ± 4.32. The average fluorescence intensity of aggregated neurons, normalized to the number of aggregated cells, was 231.1 ± 14.49. These results indicated that Fyn could promote neuronal aggregation and adhesion, even when its SH2 domain was inactive.


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)

Over-expression of FynR176A induced neuronal aggregation in the DCP and IZ. (A, B) Sections of P1 brain transfected with FynR176A at E15.5 showed many aggregations formed in the DCP and IZ. (A’, B’) Higher magnification of FynR176A positive neurons formed aggregations in the DCP and IZ. The arrow points to the GFP+/DAPI+/Brn2+ (red). (A, B) Scale bar = 100 μm, (A’) Scale bar = 20 μm, (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 002: Over-expression of FynR176A induced neuronal aggregation in the DCP and IZ. (A, B) Sections of P1 brain transfected with FynR176A at E15.5 showed many aggregations formed in the DCP and IZ. (A’, B’) Higher magnification of FynR176A positive neurons formed aggregations in the DCP and IZ. The arrow points to the GFP+/DAPI+/Brn2+ (red). (A, B) Scale bar = 100 μm, (A’) Scale bar = 20 μm, (B’) Scale bar = 10 μm.
Mentions: Our study showed that overexpression of the SH2 domain mutant form of Fyn also induced neuronal aggregation in the CP and IZ of mouse cerebral cortex (Fig. 2). The upper layer neuronal marker ‘Brn2’ staining suggested that the aggregated neurons in the CP/IZ belonged to layer II/III. The aggregation zone was packed densely with cells and clearly demarcated from the surroundings. There was an average of six aggregations in every section. The average cell number in the aggregation zone was 18.6 ± 4.32. The average fluorescence intensity of aggregated neurons, normalized to the number of aggregated cells, was 231.1 ± 14.49. These results indicated that Fyn could promote neuronal aggregation and adhesion, even when its SH2 domain was inactive.

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