The Mental Retardation-Associated Protein srGAP3 Regulates Survival, Proliferation, and Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

Lü, Haixia; Jiao, Qian; Wang, Yuanyuan; Yang, Zhiqian; Feng, Minjuan; Wang, Li; Chen, Xinlin; Jin, Weilin; Liu, Yong

doi:10.1089/scd.2012.0455

Cited by 17 publications

(19 citation statements)

References 32 publications

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“…NSCs/NPCs were isolated from cerebral cortex of rat embryos on embryonic day 14 (E14) to 15 (E15) and cultured in serum-free growth medium following the protocol of Gage et al (1995) and optimized in our lab (Lu et al, 2011, 2013). NSCs/NPCs growth medium contains DMEM/F12 (Dulbecco’s modified Eagle medium and Ham’s F12, 1:1), 10 ng/mL bFGF, 20 ng/mL EGF, 100 U/mL penicillin, 100 μg/mL streptomycin, 1% N2 and 2% B27 supplement (all from Invitrogen, Carlsbad, CA, USA) and 2.5 μg/mL heparin (Sigma, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Immunocytochemistry staining was performed following standard protocol and optimized in author’s laboratory (Lu et al, 2011, 2013). Primary antibodies, including monoclonal mouse anti-nestin (1:200, Millipore, Temecula, CA, USA), monoclonal mouse anti-β-tubulin III (1:200, Millipore, Temecula, CA, USA) and monoclonal mouse anti-GFAP (1:500, Millipore, Temecula, CA, USA) were used to identify NSCs/NPCs, neurons, astrocytes, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

Jiao

et al. 2017

Front. Cell. Neurosci.

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Cell-cell interaction as one of the niche signals plays an important role in the balance of stem cell quiescence and proliferation or differentiation. In order to address the effect and the possible mechanisms of cell-cell connection on neural stem/progenitor cells (NSCs/NPCs) proliferation and differentiation, upon passaging, NSCs/NPCs were either dissociated into single cell as usual (named Group I) or mechanically triturated into a mixture of single cell and small cell clusters containing direct cell-cell connections (named Group II). Then the biological behaviors including proliferation and differentiation of NSCs/NPCs were observed. Moreover, the expression of gap junction channel, neurotrophic factors and the phosphorylation status of MAPK signals were compared to investigate the possible mechanisms. Our results showed that, in comparison to the counterparts in Group I, NSCs/NPCs in Group II survived well with preferable neuronal differentiation. In coincidence with this, the expression of connexin 45 (Cx45), as well as brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in Group II were significantly higher than those in Group I. Phosphorylation of ERK1/2 and JNK2 were significantly upregulated in Group II too, while no change was found about p38. Furthermore, the differences of NSCs/NPCs biological behaviors between Group I and II completely disappeared when ERK and JNK phosphorylation were inhibited. These results indicated that cell-cell connection in Group II enhanced NSCs/NPCs survival, proliferation and neuronal differentiation through upregulating the expression of gap junction and neurotrophic factors. MAPK signals- ERK and JNK might contribute to the enhancement. Efforts for maintaining the direct cell-cell connection are worth making to provide more favorable niches for NSCs/NPCs survival, proliferation and neuronal differentiation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

Jiao

et al. 2017

Front. Cell. Neurosci.

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“…A first analysis of the gross morphology of the DG revealed that the thickness of the granule layer was not significantly altered in SrGAP3-deficient mice, indicating that no major cell loss occurred in this area. However, it might be possible that adult neurogenesis within the hippocampus is affected in these mice, since it has been shown that knockdown of SrGAP3 down-regulates the number of cortical neuronal stem cells, derived from embryonic rats (E14) in vitro (Lu et al 2013). Furthermore, conditional SrGAP3 knockout mice were previously shown to display mislocated DCX positive cells in the corpus callosum that are thought to stem from the subventricular zone (Kim et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has been shown in vitro that lentivirus-mediated knockdown of SrGAP3 dramatically decreases viability and proliferation of cortical immature neural stem cells/neural progenitor cells (Lu et al 2013). Aside from the SVZ, the dentate gyrus (DG) is also capable of adult neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

Morphological and behavioral characterization of adult mice deficient for SrGAP3

et al. 2016

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SrGAP3 belongs to the family of Rho GTPase proteins. These proteins are thought to play essential roles in development and in the plasticity of the nervous system. SrGAP3-deficient mice have recently been created and approximately 10 % of these mice developed a hydrocephalus and died shortly after birth. The others survived into adulthood, but displayed neuroanatomical alteration, including increased ventricular size. We now show that SrGAP3-deficient mice display increased brain weight together with increased hippocampal volume. This increase was accompanied by an increase of the thickness of the stratum oriens of area CA1 as well as of the thickness of the molecular layer of the dentate gyrus (DG). Concerning hippocampal adult neurogenesis, we observed no significant change in the number of proliferating cells. The density of doublecortin-positive cells also did not vary between SrGAP3-deficient mice and controls. By analyzing Golgi-impregnated material, we found that, in SrGAP3-deficient mice, the morphology and number of dendritic spines was not altered in the DG. Likewise, a Sholl-analysis revealed no significant changes concerning dendritic complexity as compared to controls. Despite the distinct morphological alterations in the hippocampus, SrGAP3-deficient mice were relatively inconspicuous in their behavior, not only in the open-field, nest building but also in the Morris water-maze. However, the SrGAP3-deficient mice showed little to no interest in burying marbles; a behavior that is seen in some animal models related to autism, supporting the view that SrGAP3 plays a role in neurodevelopmental disorders.

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“…These proteins were identified as the downstream regulators of the Slit and Robo receptor system and are important in numerous developmental processes in diverse cell types (1–3). During neural development, srGAP1, 2 and 3 are widely expressed in the nervous system and function as multifunctional adaptor proteins involved in neuronal migration, neuronal morphogenesis, neurite outgrowth and synaptic plasticity (1,3–8). …”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of srGAP2 in cell nuclei and cytoplasm during the differentiation of rat neural stem cells in vitro

Jiao

Wang

Zhang

et al. 2016

Molecular Medicine Reports

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Different SLIT-ROBO Rho GTPase-activating proteins (srGAPs) have different levels of expression and diverse functions during neural development. Although srGAP2 is expressed in developmental brain tissue, little is known about its influence on cellular development of the nervous system. In the current study, dynamic expression of endogenous srGAP2 during neural stem cell/progenitor cell (NSC/NPC) differentiation in vitro was investigated in order to elucidate the association between the dynamic expression of srGAP2 and neural development. srGAP2 was expressed in undifferentiated NSCs/NPCs, and differentiated neurons and astrocytes with distinct expression patterns. In conjunction with the differentiation of NSCs/NPCs in vitro, the number of srGAP2+ cells markedly reduced. The percentage of srGAP2+ cells in the population of nestin+ and β-tubulin III+ cells was significantly downregulated while in the population of glial fibrillary acidic protein-positive cells, almost all cells were srGAP2+. srGAP2 was predominantly expressed in the cell nucleus in all cell types. srGAP2 was also weakly expressed in the cytoplasm of nestin+ and β-tubulin III+ cells at 3 and 7 days in vitro. However levels were gradually downregulated during the process of differentiation and almost disappeared in β-tubulin III+ cells at 14 days. The results from the present study suggest that srGAP2 is involved in regulating NSC/NPC differentiation during neural development. The translocation of srGAP2 in the cytoplasm and cell nucleus in different cell types may function as a director in decisions regarding cell fate.

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The Mental Retardation-Associated Protein srGAP3 Regulates Survival, Proliferation, and Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

Cited by 17 publications

References 32 publications

Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

Morphological and behavioral characterization of adult mice deficient for SrGAP3

Dynamic expression of srGAP2 in cell nuclei and cytoplasm during the differentiation of rat neural stem cells in vitro

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