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Arnold Kriegstein, MD, PhD

Arnold Kriegstein, MD, PhD
Director, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Neurology
Research Summary:

Neural Stem Cells and Embryonic Cortical Development

Research in our lab focuses on the way in which neural stem and progenitor cells produce neurons, and ways in which this information can be used for cell based therapies to treat diseases of the nervous system. We found that radial glial cells, long thought to simply guide nerve cells during migration, are neuronal stem cells in the developing brain. We also found a second type of nerve cell precursor produced by radial glial cells suggesting a new mechanism for the generation of cell diversity and potential new strategies for generating specific neuronal subtypes. Recent insights gained from studies of the developing human cerebral cortex are illuminating potential evolutionary steps that contributed to structural and functional features of the human brain, as well as neurodevelopmental events that underlie a spectrum of cortical disorders including autism, schizophrenia, and epilepsy. Unlike the developing rodent cortex, the developing human cortex contains a massively expanded outer proliferative zone that is thought to account for the bulk of cortical neurogenesis. We have begun to characterize the types of progenitor cells within this progenitor region, to determine the genetic profiles of specific progenitor populations, and to explore how these cells contribute to the huge expansion of neuron number that characterizes the human cerebral cortex.

Selected Publications

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., Martínez-Cerdeño, 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.

Hansen, D.V., Lui, J.H., Parker, P.R., Kriegstein, A.R., Neurogenic radial glia in the outer subventricular zone of human neocortex, Nature, 464:554-561, 2010.

Wang, X., Tsai, J.W., LaMonica, B., Kriegstein, A.R., A new subtype of progenitor cell in the mouse embryonic neocortex, Nature Neuroscience, 14:555-61, 2011.

Lui, J.H., Hansen, D.V., Kriegstein, A.R., Development and Evolution of the Human Neocortex, Cell, 146:18-36, 2011.

Lamonica BE, Lui JH, Hansen DV, Kriegstein AR., Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex. Nature Commun. 4:1665, 2013.

Hansen DV, Lui JH, Flandin P, Yoshikawa K, Rubenstein JL, Alvarez-Buylla A, Kriegstein AR. Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences. Nature Neuroscience, 11:1576-87, 2013.