Epha4 gene regulates corticogenesis through FGF signaling

doi:10.3877/cma.j.issn.2095-1221.2017.05.002

Abstract

Abstract:

Objective

To illuminate the function ofEpha4gene in RGC cell fate determination during early corticogenesis.

Methods

Epha4gene was deleted in cortical cells at E11.5 or E13.5 using Cre-loxp method. The mice were divided into 3 groups: Group A (control mice), Group B (Nestin; Epha4fx/fxmutant mice) and Group C (GFAP; Epha4fx/fxmutant mice). Nissle staining was used to analyze the morphological changes of the mutant mice. Co-immunofluoresence was used to determine the proliferation and differentiation of RGC. Western blotting was used to detect the signaling pathway in the mutant mice. And the statistical analysis was achieved using Student'st-test.

Results

Nissle stainingshowed the size of the cerebral cortex at P0 was smaller than that of controls whenEpha4was deleted at E11.5 (475±66μmvs709±30μm,P < 0.05) but not when it was deleted at E13.5 (727±37μmvs709±30μm,P > 0.05). BrdU labeling followed by co-immunofluoresence showed the proliferation ability of RGC decreased (Nestin; Epha4fx/fx 46±1﹪ vs Epha4fx/fx 58±2﹪,P < 0.05;GFAP;Epha4fx/fx 50±2﹪ vs Epha4fx/fx 58±2﹪,P < 0.05), while the differentiation ability of RGC increased (Nestin; Epha4fx/fx 34±5﹪ vs Epha4fx/fx 25±1﹪,P < 0.05;GFAP;Epha4fx/fx 35±2﹪ vs Epha4fx/fx 25±1﹪,P < 0.05). Western blotting showed cortical cells from both deletion mutants revealed lower phosphorylation of ERK and FRS2αin the presence of FGF.

Conclusion

Epha4gene, in cooperation with an FGF signal, contributes to function in RGC cell fate determination during early corticogenesis. These findings provide important molecular evidence for the clinical treatment of neurodegenerative diseases such as spinal cord injury and Alzheimer disease.

Key words: Cerebral cortex, Glial cells, Epha4, FGF, Signal pathway, Cre-loxp

Qingfa Chen, Fabin Han. Epha4 gene regulates corticogenesis through FGF signaling[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2017, 07(05): 259-264.

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Figures/Tables 7

References 14

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组别	动物数	皮层厚度	VZ+SVZ厚度
对照组	5	709±30	65± 4
Nestin；Epha4（fx/fx）	5	475±66^a	39±13^a
GFAP；Epha4（fx/fx）	5	727±37^b	63± 8^b
F值	?	44.75	12.61
P值	?	< 0.01	< 0.01

组别	动物数	皮层厚度	VZ+SVZ厚度
对照组	5	709±30	65± 4
Nestin；Epha4（fx/fx）	5	475±66^a	39±13^a
GFAP；Epha4（fx/fx）	5	727±37^b	63± 8^b
F值	?	44.75	12.61
P值	?	< 0.01	< 0.01

组别	动物数	Ki67+BrdU+细胞占总BrdU+细胞的比例	Tuj1+BrdU+细胞占总BrdU+细胞的比例
对照组	5	58±2	25±1
Nestin；Epha4（fx/fx）	5	46±1^a	34±5^a
GFAP；Epha4（fx/fx）	5	50±2^ab	35±2^a
F值	?	62.22	15.17
P值	?	<0.01	<0.01

组别	动物数	Ki67+BrdU+细胞占总BrdU+细胞的比例	Tuj1+BrdU+细胞占总BrdU+细胞的比例
对照组	5	58±2	25±1
Nestin；Epha4（fx/fx）	5	46±1^a	34±5^a
GFAP；Epha4（fx/fx）	5	50±2^ab	35±2^a
F值	?	62.22	15.17
P值	?	<0.01	<0.01

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