Scientists at the Salk Institute for Biological Studies have identified a crucial cellular signal that controls the fate of stem cells in the brains of adult mice.
After these stem cells divide, they have to choose between several options - remaining a stem cell, turning into a nerve cell, also called a neuron, or becoming part of the brain's support network of cells called astrocytes or oligodendrocytes. According to a study published in this week's Nature, the decision to become a neuron is controlled by Wnt3 signaling molecules, which are secreted by neighboring astrocytes.
Like an unmolded block of clay, adult stem cells in the brain harbor the potential to turn into mature functioning brain cells but require additional nudging by their local microenvironment to turn into fully specialized or differentiated cells. The "nudging" comes in the form of chemical signals, but the identity of these cues is largely unknown.
"In an earlier study with Hong Jun Song, a co-author on this paper and now an assistant professor at Johns Hopkins University, we co-cultured neuronal stem cells with neurons, which gave rise to oligodendrocytes, but the same stem cells co-cultured with astrocytes isolated from the hippocampus gave rise to neurons," says Fred H. Gage, Professor in the Laboratory of Genetics at the Salk Institute and the lead author of the study.
After a lengthy and trying search, the co-first authors D. Chichung Lie, now at the GSF-National Research Center in Munich, Germany, and Sophia A. Colamarino, who since became the Scientific Director of Cure Autism Now, finally pinpointed Wnt3 as the persuasive signal molecule secreted by the astrocytes.
Wnt proteins form a family of highly conserved signaling molecules that play a crucial role in controlling cell expansion and lineage decisions in many types of stem cells.
"We blocked Wnt3 in the brain of mice with the help of molecular tools used for gene therapy, and neurogenesis decreased dramatically. When we added additional Wnt3, the number of neurons increased," explains Gage. "This increase proved to us that the Wnt signal is really important in vivo and not just a tissue culture artifact."