Why humans have such big, complex brains – Development of the Neocortex
Hansen DV, Lui JH, Parker PR, Kriegstein AR. 2010. Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature. 464(7288):554-561.
Wang X, Tsai JW, LaMonica B, Kriegstein AR. 2011. A new subtype of progenitor cell in the mouse embryonic neocortex. Nat Neurosci. 14(5):555-61.
Supportive Articles: Lui JH, Hansen DV, Kriegstein AR. 2011. Development and evolution of the human neocortex. Cell. 146(1):18-36.
Briefly tell us a bit about yourself, your career path over the years, and specifically what brought you to begin working on neocortex development.
You conclude in your most recent paper that oRG cells originate from radial glial cells. Do you yet know what mechanism causes some radial glia to differentiate this way, while others commit to traditional radial glial fates?
Does the amount of cell divisions of a single oRG progenitor differ between the mouse and human, or is the ratio of progenitors to non-progenitors causing the difference in brain size?
You discuss the phases of the cell cycles of radial glia cells relative to their movements from the apical surface towards the basal lamina. What signals are at play to causes these changes in the cell cycle relative to location? Effectively, how does the cell “know” when to be in G1, G2, or S phase? Are there any known long-range diffusible signals regulating this process or other aspects of radial glial development?
In Figure 3 of the paper A new subtype of progenitor cell in the mouse embryonic neocortex, you showed that oRG cells undergo asymmetric division to generate a new oRG cell and a daughter neuron cell. In b, this process seemed to take up to 40 hours to complete, whereas in c, this process only took 22 hours. So is there a temporal control in the division of these cells, and how is it affecting their proliferation rate?
You demonstrated that oRG cells are rare in the rodent cortex but they exist in a lateral to medial gradient. We know that, likely as a result of selective pressure, humans have a much higher concentration of oRG cells, but are human oRG cells also present in a gradient?
What obstacles did you overcome in the process of getting human cortical tissue? Are you planning on continuing any studies with it?
Before it was known that neurons in the cortex migrate towards the cortical plate, and now you have discovered that neurons can migrate laterally as well. Is there any indication, or chance, that some cells could be migrating away from the cortical plate? Or backwards, per se?
Have any developments been made in characterizing functional differences between the progeny of outer radial glia and standard traditional radial glia?
You show that “mouse oRG cells undergo self-renewing asymmetric division to generate neurons directly, whereas human oRG cells generate transit-amplifying cells.” What do you think is the evolutionary advantage of that distinction?