Like a house being built from the inside out, brain development must proceed in a precise order. Otherwise, everything falls apart. The brain is constructed from neural progenitor cells, which give rise to all the neuron types found in the cerebral cortex. Now scientists have now found that these cells are the architects as well, determining which layers of the cerebral cortex are assembled during various points in development. Researchers say the finding places important restrictions on the potential therapeutic use of neural stem cells.
When most body cells divide, they give rise to identical offspring, but--at least in invertebrates--neural progenitor cells divide "asymmetrically," producing two cell types at once. The stage of neural development determines which types of cells are made. Neuroscientists led by Qin Shen and Sally Temple, both of Albany Medical College in New York, wanted to see if the same holds true for vertebrate neural progenitor cells.
The team set up a microscope and video camera over several culture dishes, each containing a single neural progenitor cell taken from a mouse embryo 10 days after fertilization. Labeled antibodies, which bind to specific cell types, allowed the researchers to determine which types of neuron were being created at which times.
Even in a dish, the progenitor cells divided asymmetrically. This produced the proper layers of neurons in the same order they arise in living animals. Timing was key: The older the progenitor cells were, the less able they were to give rise to the innermost neuron types. This programming, says Shen, helps ensure that the proper brain layers form at the right moment. The team reported its findings online yesterday in Nature Neuroscience.
"It's a landmark paper," says developmental neuroscientist Susan McConnell of Stanford University. The observation of a cut-off point at which the progenitor cells cannot make some neuron types extends "a word of caution for people interested in using stem cells" to resolve neurological problems, says neuroscientist Paula Monaghan of University of Pittsburgh in Pennsylvania. Because older progenitor cells cannot make the range of neurons a younger cell can give rise to, she says, "the source of stem cells is going to be important."