Cold Spring Harbor, NY Researchers at Cold Spring Harbor Laboratory (CSHL) have solved an important piece of one of neuroscience's outstanding puzzles: how progenitor cells in the developing mammalian brain reproduce themselves while also giving birth to neurons that will populate the emerging cerebral cortex, the seat of cognition and executive function in the mature brain.
CSHL Professor Linda Van Aelst, Ph.D., and colleagues set out to solve a particular mystery concerning radial glial cells, or RGCs, which are progenitors of pyramidal neurons, the most common type of excitatory nerve cell in the mature mammalian cortex.
In genetically manipulated mice, Van Aelst's team demonstrated that a protein called DOCK7 plays a central regulatory role in the process that determines how and when an RGC "decides" either to proliferate, i.e., make more progenitor cells like itself, or give rise to cells that will mature, or "differentiate," into pyramidal neurons. The findings are reported in the September 2012 issue of Nature Neuroscience.
DOCK7 was already known to be highly expressed in various parts of the developing rodent brain, including the hippocampus and cortex. It had been shown by Van Aelst and colleagues to control the formation of axons wiring that connects neurons.
Balancing proliferation and differentiation
In their newly published research, Van Aelst, along with Drs. Yu-Ting Yang and Chia-Lin Wang, a graduate student and postdoctoral fellow, respectively, in the Van Aelst lab, elucidate DOCK7's regulatory role in experiments in which the protein was alternately silenced and overexpressed.
When the protein was silenced in mouse embryos, neuronal differentiation was impeded; RGCs remained in their progenitor state. When DOCK7 was overexpressed, RGCs differentiated prematurely, resulting in more neurons and fewer RGCs.
These and related experiments revealed the mechanism t
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Cold Spring Harbor Laboratory