Regulation neuraler Stammzellen durch Extrazellulärmatrix (EZM)-gesteuerte GEFs

• Antragsteller: Professor Dr. Andreas Faissner
• Fachliche Zuordnung: Kognitive, systemische und Verhaltensneurobiologie
• Förderung: Förderung von 2010 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 182024211

• Erstellungsjahr: 2016

Zusammenfassung der Projektergebnisse

Small GTP-cleaving enzymes (GTPases) of the RhoA-subfamily play manifold roles in cell biology and are regulated by upstream nucleotide exchange factors (GEFs). In the present project, we focused on the GEFs of the Vav-subfamily that were originally described as proto-oncogenes of the hematopoetic system. In particular the GEF Vav3 is expressed in the developing nervous system and plays important roles during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes. We highlight its regulatory role for progenitor differentiation in the developing retina and the maturation of neural stem cells of the developing embryonic cortex of the mouse brain. We propose that Vav3 mediates the response of neural stem and glial progenitor cells to environmental cues.

Projektbezogene Publikationen (Auswahl)

• (2010) Chondroitin sulfates are required for fibroblast growth factor-2-dependent proliferation and maintenance in neural stem cells and for epidermal growth factordependent migration of their progeny. Stem Cells 28:775-787
  Sirko S, von Holst A, Weber A, Wizenmann A, Theocharidis U, Gotz M, Faissner A
  
• (2010) Expression of NMDA receptors and Ca2+-impermeable AMPA receptors requires neuronal differentiation and allows discrimination between two different types of neural stem cells. Cell Physiol Biochem 26:935-946
  Muth-Kohne E, Pachernegg S, Karus M, Faissner A, Hollmann M
  
• (2010) Integrin activation or alpha 9 expression allows retinal pigmented epithelial cell adhesion on Bruch's membrane in wet age-related macular degeneration. Brain 133:448-464
  Afshari FT, Kwok JC, Andrews MR, Blits B, Martin KR, Faissner A, Ffrench-Constant C, Fawcett JW
  
• (2010) Regulatory mechanisms that mediate tenascin C-dependent inhibition of oligodendrocyte precursor differentiation. J Neurosci 30:12310-12322
  Czopka T, von Holst A, ffrench-Constant C, Faissner A
  
• (2011) Structurally Distinct LewisX Glycans Distinguish Subpopulations of Neural Stem/Progenitor Cells. J Biol Chem 286:16321-16331
  Hennen E, Czopka T, Faissner A
  
• (2011) The extracellular matrix molecule tenascin-C modifies expression levels and territories of key patterning genes during spinal cord astrocyte specification. Development 138: 5321-5331
  Karus M, Denecke B, ffrench-Constant C, Wiese S, Faissner A
  
• (2012) Normal Sulphation levels regulate spinal cord neural precursor cell proliferation and differentiation. Neural Dev 7:20
  Karus M, Samtleben S, Busse C, Tsai T, Dietzel ID, Faissner A, Wiese S
  (Siehe online unter https://doi.org/10.1186/1749-8104-7-20)
• (2012) Tenascin C regulates proliferation and differentiation processes during embryonic retinogenesis and modulates the de-differentiation capacity of Muller glia by influencing growth factor responsiveness and the extracellular matrix compartment. Dev Biol 369:163-176
  Besser M, Jagatheaswaran M, Reinhard J, Schaffelke P, Faissner A
  (Siehe online unter https://doi.org/10.1016/j.ydbio.2012.05.020)
• (2013) A LewisX glycoprotein screen identifies the low density lipoprotein receptorrelated protein 1 (LRP1) as a modulator of oligodendrogenesis in mice. J Biol Chem 288:16538-16545
  Hennen E, Safina D, Haussmann U, Worsdorfer P, Edenhofer F, Poetsch A, Faissner A
  (Siehe online unter https://doi.org/10.1074/jbc.M112.419812)
• (2013) Differential Expression of Micro-Heterogeneous LewisX-Type Glycans in the Stem Cell Compartment of the Developing Mouse Spinal Cord. Neurochemical research 38:1285-1294
  Karus M, Hennen E, Safina D, Klausmeyer A, Wiese S, Faissner A
  (Siehe online unter https://doi.org/10.1007/s11064-013-1048-6)
• (2015) Erratum to: The guanine nucleotide exchange factor Vav3 regulates differentiation of progenitor cells in the developing mouse retina. Cell Tissue Res 360:431-433
  Luft V, Reinhard J, Shibuya M, Fischer KD, Faissner A
  (Siehe online unter https://doi.org/10.1007/s00441-015-2160-5)
• (2015) The guanine nucleotide exchange factor Vav3 regulates differentiation of progenitor cells in the developing mouse retina. Cell Tissue Res 359:423-440
  Luft V, Reinhard J, Shibuya M, Fischer KD, Faissner A
  (Siehe online unter https://doi.org/10.1007/s00441-014-2050-2)
• (2016) Low-density lipoprotein receptor-related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation. Glia 64:1363-80
  Safina D, Schlitt F, Romeo R, Pflanzner T, Pietrzik CU, Narayanaswami V, Edenhofer F, Faissner A
  (Siehe online unter https://doi.org/10.1002/glia.23009)
• (2016) Regulation of oligodendrocyte precursor maintenance by chondroitin sulphate glycosaminoglycans. Glia 64:270-286
  Karus M, Ulc A, Ehrlich M, Czopka T, Hennen E, Fischer J, Mizhorova M, Qamar N, Brustle O, Faissner A
  (Siehe online unter https://doi.org/10.1002/glia.22928)