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Neuroscience Graduate Program at UCSF
Neural Stem Cells and Embryonic Cortical Development
The process by which neurons are born and migrate to the cortex is of fundamental importance to a wide range of neurodevelopmental disorders including birth defects, schizophrenia, epilepsy, and learning disabilities. We are using electrophysiological, optical recording, and molecular biological apporaches to study intercellular signaling and proliferation in the embryonic cerebral cortex during fetal stages of development. Findings from our laboratory reveal that embryonic neuronal stem cells appear to be highly interactive, communicating with each other directly through gap junction channels and responding to their local environment through specific neurotransmitter receptors. In addition, we recently demonstrated that radial glial cells, present only in the embryonic and fetal developing brain and long thought to simply guide embryonic nerve cells during migration, are neuronal stem cells in the developing brain. We found that radial glial cells divide to produce nerve cells that often climb along their parent radial glial cells to reach the developing cerebral cortex. This finding suggests that a radial glial 'mother' cell generates and guides daughter neurons. More recently, we have found a second nerve cell precursor in the embryonic brain that undergoes a different mode of cell division in a distinct proliferative zone. This suggests new mechanisms for the generation of cell diversity in the developing cortex. The identification of the radial glial cell as a key neuronal stem cell in the developing brain has helped shift attention to the role of glial cells as neuronal stem cells in the adult brain, and has the potential to lead to innovative therapies aimed at treating diseases of brain injury.
Willian Walantus
Ashkan Javaherian
David Castaneda-Castellanos
Tristan Sands
Laura Elias
Jeanelle Agudelo
Doris Wang
Corey Harwell
Philip Parker
Jan Lui
Noctor, S.C., Flint, A.C., Weissman, T.A., Dammerman, R.S., & Kriegstein, A.R., Neurons derived from radial glial cells establish radial units in neocortex, Nature, 409: 714-20, 2001
Noctor, S.C., Martinez-Cerdeno, V, Ivic, L, Kriegstein, A.R., Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases, Nature Neuroscience, 7:136-44, 2004.
Weissman T.A., Riquelme P.A., Ivic L., Flint A.C., Kriegstein, A.R., Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex, Neuron, 43:647-61, 2004
Arnold R. Kriegstein, M.D./Ph.D.
Phone
415-476-0766
Physical Address
HSW-1201F
513 Parnassus
Mailing Address
UCSF
513 Parnassus,
Box 0525
San Francisco, CA 94143-0525
For Internal Campus Mail
Box 0525
Other Websites
Institute for Regeneration MedicinePIBS Website