Adult Neural Stem Cells
Kriegstein A, Alvarez-Buylla A. 2009. The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci. 32:149-84.
Jackson EL, Alvarez-Buylla A. 2008. Characterization of adult neural stem cells and their relation to brain tumors. Cells Tissues Organs. 188(1-2):212-24.
Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, Schneider-Maunoury S, Alvarez-Buylla A. 2008. Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci. (3):277-84.
Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. 2008. Neural Stem Cells Confer Unique Pinwheel Architecture to the Ventricular Surface in Neurogenic Regions of the Adult Brain. Cell Stem Cell. 3(3):265-78.
Please tell us a bit about yourself and your research and how you got started in the field of neural stem cells.
Can you please summarize for us the structural characteristics of the Adult Neural Stem Cell Niche and how its organization helps to foster Stem cell renewal and also Neurogenic and Gliogenic properties?
Drawing on the discussion from your Stem Cell journal paper, can you please elaborate on how the contacts made between B1 cells and neural vasculature might influence development, differentiation, and/or proliferation of adult neural stem cells? What factors specifically come into play here?
In general what do you see as the role of cilia in adult stem cell function? Specifically, B2 cells are described as Astrocytes with multipolar morphology. How does the multipolar morphology of B2 cells effect its location?
The hGFAP::Cre;Kif3afl/fl mice suffered from a smaller SGZ, suggesting that primary cilia do in fact play a role in the proliferation of progenitor cells. However, it was also observed that a small population of BrdU-stained cells survived in the granular zone. Did these cells appear simply because they developed earlier or is it possible they are a different subpopulation of cells.
It seems like B cells are derived from an astrocytic lineage and may be due to the transition of late radial glial cells into astrocytes, especially since they express the astroglial markers GFAP and GLAST. To the best of your knowledge, is there any way to further discern the B cell population from the astroglial lineage, perhaps the down regulation of radial glial specific markers when B cells become present in the CNS?
What are the rates of Neurogenesis as organisms reach adulthood compared to embryonic and postnatal neurogenesis? Why do you think lifelong neurogenesis has been conserved in the dentate gyrus of the human hippocampus, while almost all other areas of the brain have no adult neurogenesis? How does this specifically support continuous learning and memory?
Yvanka De Soysa
What is the purpose of interkinetic nuclear migration during radial glial development? And what mechanisms control this behavior?
Shh signaling is known to function as a morphogen during early development. Is Shh also signaling in a graded fashion over the stem cell niche? Are the Cilia in a particularly appropriate position to receive these Shh signals?
In the Nature Neuroscience paper, you mention that the loss of Kif3a function in ASC proliferation can rescue some of the effects of loss of Smoothened expression, due to Kif3a’s role in Shh signaling. Why does this loss of two required elements actually help to reduce phenotypic severity, instead of making it worse?
Would you expect the hGFAP::Cre; Kif3afl/fl mice to exhibit mental retardation, cognitive deficits, or a shorter life expectancy had they not been sacrificed? Would these mice be a good model for severe cognitive deficits in humans?
Currently in your opinion what are the most pressing questions in the field of Adult Stem Cell Research and their use in human disease therapy, and what steps is your lab taking to address those questions?