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Neural Stem Cells and Glial Progenitors

Biology of neural stem/progenitor cells, glial progenitors and their niches:

The CNS originates from a layer of neuroepithelial cells that expand by symmetric division. With increasing thickness of the walls of the neural tube the neuroepithelium evolves to radial glia (RG). These proliferate and self-renew by symmetric division, but progressively give rise to neurons that are generated in an asymmetric division mode. Thereby, radial glia cells do give rise to neurons in vitro and serve as neural stem/progenitor cells (NSPCs). Following neurogenesis, oligodendrocyte precursors are formed and migrate to target regions to myelinate the axonal connections. Finally, the radial glia recedes and transforms into astrocytes, with two well-known exceptions, the Bergman glia of the cerebellum and the Müller glia of the retina. In the adult CNS, neurogenesis is limited to two canonical regions, that is the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampus. There, progeny of the radial glia is thought to reside as radial-type astrocytes in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus of the hippocampus, where these cells serve as stem cells for neurogenesis in the adult CNS. It is widely accepted that these neurogenic territories harbour specialized environments that sustain NSPCs and are regarded as niches which function as integrative entities for a large number of physiological stimuli.

The adult stem cell niche in the wall of the lateral ventricle is characterized by a combination of factors i) delivered by the cerebrospinal fluid, ii) originating from the blood or endothelial cells and iii) produced by cells that reside within or adjacent to the niche. The laboratory studies the implications of this concept in detail focuses on the extracellular matrix (ECM) of the stem cell niche. Special emphasis is given to glycoproteins, e.g. tenascin-C and chondroitinsulfate proteoglycans of the niche. The significance of these components for the differentiation of glial progenitors, namely astrocytes and oligodendrocyte precursors and their roles for myelination during development and in conditions of disease are also themes of the laboratory. Another aspect of the work concerns the expression of these ECM molecules in glial tumors and their potential effects on tumor stem cells of the nervous system. Finally, the response of the stem cell niche to lesions and the potential use of stem cells for regeneration and repair of the CNS are topics of the laboratory.

Additionally to extracellular molecules that affect the cells, the interaction with these molecules is of major interest for the department. In this context a transmembrane receptor that triggers differentiation of glia cells needs to be mentioned: LRP1 (low-density lipoprotein receptor-related protein 1). LRP1 is a ubiquitously expressed receptor that can bind up to 40 different ligands, such as integrins, matrix molecules and growth factors. Here we concentrate on the function of this receptor in central nervous system development with special focus on glia cells, such as radial glia, astrocytes and oligodendrocytes.

Past and current funding: DFG (Fa 159/16-1; vHo 2476/1-3), BMBF, Mercator Research Foundation and Land NRW.



Dr. Kristin Glotzbach