Zellmorphologie und Molekulare Neurobiologie
Faculty of Biology and Biotechnology

Research program

Glial Recognition Molecules in Neural Pattern Formation and regeneration

Astrocytes play an important role in forming neural tissues, for example by guiding migrating neurons and growth cones to their destination or by forming transient tissue boundaries designed to segregate neuronal assemblies.

In the adult CNS, reactive astrocytes emmerge as key components of the astroglial scar after lesioning and form an important obstacle for regeneration. The laboratory focusses on the identification of glial molecules which might mediate these morphogenetic functions and has shown that constituents of the neural extracellular matrix (ECM) play various roles in this context. Tenascin-C (TN-C) glycoproteins represent one of the most abundant glycoproteins of the neural ECM. TN-C glycoproteins are transiently expressed by astrocytes during CNS development and consist structurally of EGF-type repeats, fibronectin-type-III (FNIII) modules and homologies to fibrinogen.

On the mRNA-level, we have recently found a large number of isoforms which are generated by a combinatorial re-arrangement of FNIII domains at a unique splice site. Distinct FNIII-modules of TN-C contain binding sites for various receptors and are involved in neuron binding, neuron migration and axon outgrowth. One of several isoforms reacts specifically with the Ig-superfamily member Contactin/F3 and induces neurite outgrowth promotion in embryonic hippocampal neurons. In some regions, TN-C co-localizes with the chondroitin sulfate proteoglycan (CSPG) DSD-1-PG/phosphacan which represents a splice variant of receptor phosphotyrosine phosphatase (RPTP) beta/zeta. This receptor is expressed by glial cells and occurs in two isforms named RPTP-beta(l) and RTP-beta(s). Phosphacan binds to TN-C and the RPTP-beta isoforms might function as glial transmembrane receptors of the glycoprotein. The CSPG carries the DSD-1-epitope, a glycosaminoglycan modification which is specifically recognized by mAb 473HD and is by itself sufficient to stimulate neurite outgrowth.

The roles of these constituents are currently being investigated with regard to axon growth and guidance, the development of the visual projection, the regulation of neural progenitor cell proliferation and differentiation in a ECM-related niche, and in the framework of glial tumor cell biology. It is clear that glial cells are also involved in the response of neural tissues to lesion. The mechanisms through which glia affects neuronal behaviour in this context have only partially been elucidated. Upon infliction of a stab wound to the adult cortex, the DSD-1-epitope, the phosphacan core protein, the RPTP-beta isoforms and tenascin-C glycoproteins undergo independent and complex patterns of regulation.

The roles of these components in lesion pathology and the various regulatory factors and receptors involved will also be topics for further investigations. tors and receptors involved will also be topics for further investigations.