Loss of Shp2 within radial glia is associated with cerebral cortical dysplasia, glial defects of cerebellum and impaired sensory‑motor development in newborn mice

Zhu,Yu; Shen,Jian; Sun,Tianfu; Jiang,Hao; Xu,Kangli; Samuthrat,Thiti; Xie,Yicheng; Weng,Yuxiang; Li,Yongda; Xie,Qiangmin; Zhan,Renya

doi:10.3892/mmr.2017.8236

Loss of Shp2 within radial glia is associated with cerebral cortical dysplasia, glial defects of cerebellum and impaired sensory‑motor development in newborn mice

Authors:
- Yu Zhu
- Jian Shen
- Tianfu Sun
- Hao Jiang
- Kangli Xu
- Thiti Samuthrat
- Yicheng Xie
- Yuxiang Weng
- Yongda Li
- Qiangmin Xie
- Renya Zhan
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China, Department of Psychiatry, Kinsmen Laboratory of Neurological Research and Brain Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada, Zhejiang Respiratory Drugs Research Laboratory of China Food and Drug Administration, Laboratory Animal Center of Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
Published online on: December 11, 2017 https://doi.org/10.3892/mmr.2017.8236
Pages: 3170-3177

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Abstract

Radial glia are key neural progenitors involved in the development of the central nervous system. Tyrosine-protein phosphatase non‑receptor type 11 (Shp2) is a widely expressed intracellular enzyme with multiple cellular functions. Previous studies have revealed the critical role of Shp2 in a variety of neural cell types; however, further investigation into the function of Shp2 within radial glia is required. In the present study, a conditional knockout mouse was generated using a human glial fibrillary acidic protein (hGFAP)‑Cre driver, in which the Shp2 genes were deleted within radial glia. Loss of Shp2 within radial glia was associated with developmental retardation, postnatal lethality, reduced brain size and thinner cerebral cortices in newborn mice. Deletion of Shp2 also led to an increase in gliogenesis, a reduction in neural genesis and extracellular signal‑regulated kinase signaling within the cerebral cortex. Furthermore, glial cell defects within the cerebellum of Shp2 mutants were observed, with abnormal granular cell retention and glial cell alignment in the external granular layer. In addition, Shp2 mutants exhibited impaired sensory‑motor development. The results of the present study suggested that Shp2 may have an important role within radial glia, and regulate cerebral cortical and cerebellar development in newborn mice.

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