streifen

Project number:

402

Project title:

How do stem cells interconnect into a neuronal network?

Project supervisor:

Frances Edwards

Project description:

Most previous work on the differentiation and integration of stem cells into the brain has concentrated on one of two approaches: 1) stem cells are grown in culture and attempts are made to find growth factors etc which will make them differentiate into neurones and/or glia or 2) they are injected in vivo and clinical outcomes judged or the animal is sacrificed an the differentiation of the stem cells is studied at that end point.
By using organotypic brain slices we plan to take the advantages of both the above approaches. The organotypic slices presents neurones in a network which while in culture has much in common with the in vivo situation but in which progress of differentiation and connectivity can be monitored in detail over time.
Neurones and their synaptic connections have been shown to develop surprisingly normally under these conditions in which brain slices are made from 5 day old rats or mice and then grown in vitro.
Our preliminary data suggests that stem cells can differentiate rapidly into neurones in such a preparation and using techniques recently developed in this laboratory we will be able to study their connectivity in detail. Can a stem cell added to a slice be directed to form different types of neurone and can they connect appropriately with other neurones in the slice?

This project will start from the simplest version of using stem cells derived from adult rat hippocampus (GFP labelled) and placing them into the dentate gyrus of organotypic slices and studying thedevelopment of their phenotype and connectivity in detail. In later stages of the project attempts will be made to aim at differentiation and connectivity in other regions of the hippocampus.

Possible cortex partners for rotation:

Mart Saarma (Helsinki) testing of different growth factors to direct differentiation

Martin Schwaab (Zurich) taking the finding from the hippocampus into other tissues

Ende