Functional analysis of chrondroitin sulfates in the neural stem cell niche

• Applicant: Privatdozent Dr. Alexander von Holst
• Subject Area: Developmental Neurobiology
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 84764112

Stem cells are the cellular basis of tissue homeostasis. The stem cell niche provides the specialized environment that is able to sustain the life-long maintenance of stem cells in their discrete locations within organs. The niche consists of several different cell types and a specialized extracellular matrix (ECM) with many different constituents that include chondroitin sulfate proteoglycans (CSPGs). These carry complex sulfated carbohydrates that contribute to the functional organization of the niche by binding and sequestering many secreted growth factors. The project proposes to analyse the role of chondroitin sulfates (CS) in the neural stem cell niche with respect to the maintenance of the neural stem cell population and their differentiation into neurons and glia during development and in the adult brain. The aim of the project is to clarify the role of chondroitin sulfotransferases (CSTs), the critical synthetic enzymes for the generation of sulfated carbohydrate chains of CSPGs. This will be done by creating hypersulfated neural stem cell niches through overexpression of CSTs to increase sulfation levels at defined positions within the carbohydrate chains in vitro, in forebrain slice cultures and in vivo. It will be complemented by creating undersulfated neural stem cell niches through the loss-offunction approach by RNAi-mediated knockdown of CSTs to decrease sulfation levels at defined positions within the carbohydrate chains in vitro, in forebrain slice cultures and in vivo. This combined approach will generate evidence for (or against) the CS code hypothesis and the role defined sulfate groups in CS carbohydrate chains play for the biology of neural stem cells.

• DFG Programme: Research Grants