Michalczyk K, Ziman MNestin structure and predicted function in cellular cytoskeletal organisation. Histol Histopathol 20:665-671

School of Biomedical and Sports Science, Edith Cowan University, Joondalup, Western Australia, Australia.
Histology and histopathology (Impact Factor: 2.1). 05/2005; 20(2):665-71.
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Nestin is an intermediate filament protein expressed in dividing cells during the early stages of development in the CNS, PNS and in myogenic and other tissues. Upon differentiation, nestin becomes downregulated and is replaced by tissue-specific intermediate filament proteins. Interestingly, nestin expression is reinduced in the adult during pathological situations, such as the formation of the glial scar after CNS injury and during regeneration of injured muscle tissue. Although it is utilised as a marker of proliferating and migrating cells very little is known about its functions or regulation. In depth studies on the distribution and expression of nestin in mitotically active cells indicate a complex role in regulation of the assembly and disassembly of intermediate filaments which together with other structural proteins, participate in remodeling of the cell. The role of nestin in dynamic cells, particularly structural organisation of the cell, appears strictly regulated by phosphorylation, especially its integration into heterogeneous intermediate filaments together with vimentin or alpha-internexin.

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Available from: Melanie Ziman, Oct 04, 2015
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    • "Nestin , a class VI intermediate filament protein is expressed in the majority of mitotically active CNS and PNS progenitors that give rise to both neurons and glia ( Lendahl and McKay , 1990 ; Mujtaba et al . , 1998 ; Michalczyk and Ziman , 2005 ) and is downregulated in cells upon differentiation ( Zimmerman et al . , 1994 ; Lothian and Lendahl , 1997 ; Sahlgren et al . "
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    ABSTRACT: Radial glial cells (RGs) originally considered to provide scaffold to the radially migrating neurons constitute a heterogeneous population of the regionally variable precursor cells that generate both neurons as well as glia depending upon the location and the timing of development. Hence specific immunohistochemical markers are required to specify their spatiotemporal location and fate in the neurogenic and gliogenic zones. We hypothesize S100β as a potential and unified marker for both primary and secondary progenitors. To achieve this, cryocut sections from rat brains of varied embryonic and postnatal ages were immunolabeled with a combination of antibodies, i.e., S100β + Nestin, Nestin + GFAP and S100β + GFAP. A large population of the primary and secondary progenitors, lining the VZ and SVZ, simultaneously co-expressed S100β and nestin establishing their progenitor nature. A downregulation of both S100β and nestin noticed by the end of the 1st postnatal week marks their differentiation towards neuronal or glial lineage. In view of the absence of co-expression of GFAP (glial fibrillary acidic protein) either with S100β or nestin, the suitability of accepting GFAP as an early marker of RG's was eliminated. Thus the dynamic expression of S100β in both the neural stem cells (NSCs) and RGs during embryonic and early neonatal life is associated with its proliferative potential and migration of undifferentiated neuroblasts and astrocytes. Once they lose their potential for proliferation, the S100β expression is repressed with its reemergence in mature astrocytes. This study provides the first clear evidence of S100β expression throughout the period of neurogenesis and early gliogenesis, suggesting its suitability as a radial progenitor cell marker.
    Frontiers in Cellular Neuroscience 04/2015; 9. DOI:10.3389/fncel.2015.00087 · 4.29 Impact Factor
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    • "Thereafter, maintenance of high levels of expression was observed, indicating an efficient differentiation into the neuronal lineage. In accordance, the expression of nestin, a marker of undifferentiated NT2 cells and early neuroepithelial progenitors, was downregulated in differentiated cultures (two-fold decrease at 38DIV), while an initial four-fold increase was observed at 10DIV, probably corresponding to the proliferation of nestin + neural progenitors (Michalczyk and Ziman, 2005). At 38DIV, an extensive network of MAP2 + cells was detected throughout the neuropheres (Fig. 2d), indicating that mature neurons were present in culture at this time point. "
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    ABSTRACT: There is an urgent need for new in vitro strategies to identify neurotoxic agents with speed, reliability and respect for animal welfare. Cell models should include distinct brain cell types and represent brain microenvironment to attain higher relevance. The main goal of this study was to develop and validate a human 3D neural model containing both neurons and glial cells, applicable for toxicity testing in high-throughput platforms. To achieve this, a scalable bioprocess for neural differentiation of human NTera2/cl.D1 cells in stirred culture systems was developed. Endpoints based on neuronal- and astrocytic-specific gene expression and functionality in 3D were implemented in multi-well format and used for toxicity assessment. The prototypical neurotoxicant acrylamide affected primarily neurons, impairing synaptic function; our results suggest that gene expression of the presynaptic marker synaptophysin can be used as sensitive endpoint. Chloramphenicol, described as neurotoxicant affected both cell types, with cytoskeleton markers’ expression significantly reduced, particularly in astrocytes. In conclusion, a scalable and reproducible process for production of differentiated neurospheres enriched in mature neurons and functional astrocytes was obtained. This3D approach allowed efficient production of large numbers of human differentiated neurospheres, which in combination with gene expression and functional endpoints are a powerful cell model to evaluate human neuronal and astrocytic toxicity.
    Journal of Biotechnology 01/2015; 205. DOI:10.1016/j.jbiotec.2014.12.011 · 2.87 Impact Factor
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    • "Third-passaged ADSCs expressed some neuron-specific markers before induction by differentiation medium. Two and three weeks after neural induction in both low serum and KoSR-containing conditions, differentiated ADSCs expressed neuroepithelial transcription factor Pax6 and neural stem/progenitor cell marker Nestin (Michalczyk and Ziman, 2005). Molecular markers of early commitment to neural fates (NSE) and mature neurons Fig. 8. "
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    ABSTRACT: Neural differentiation of embryonic and adult stem cells has been reported previously. Several studies have used different proportions of serum or a cocktail of growth and differentiation factors for this purpose. In the present study we examined neural differentiation of mouse embryonic stem (ES) cells in KoSR-containing media. We also investigated neural differentiation of mouse adipose tissue-derived stem cells (ADSCs) in a medium containing KoSR, a synthetic serum replacement, and compared it with neural differentiation in low-serum condition. Meanwhile, effect of β-ME on neural differentiation was investigated in both conditions. As revealed by RT-PCR and immunocytochemistry analyses, KoSR-containing medium induced neural differentiation of mouse ES cells. Moreover, under the culture conditions we tested, ADSCs were differentiated to neuron-like cells and expressed some neuronal markers. Low concentration of β-ME improved neuron-like differentiation of the ADSCs in the 4% FBS-supplemented medium, while addition of β-ME in KoSR condition decreased neural differentiation. KoSR-containing medium without any additional factor improved generation of neuron-like cells, upregulated the expression of mature neuronal markers and led to the formation of cytoplasmic processes. In summary, our findings are indicating that mouse embryonic and mesenchymal stem cells are capable of neural development in KoSR-containing media.
    Journal of Biotechnology 12/2013; 172(1). DOI:10.1016/j.jbiotec.2013.11.028 · 2.87 Impact Factor
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