The cells of the cerebral cortex need to be generated in a timely fashion and then migrate to proper positions prior to the development of synaptic connections and functional circuits. Thus, disturbances in the proliferation, migration, or differentiation of cortical cells can lead to cognitive impairments such as those seen in Down syndrome, autism, and other developmental disabilities. The long-term objectives of this project are to identify the various stem and progenitor cells in the embryonic neocortical wall and then to characterize the molecules controlling neuronal and glial cell production from those progenitors during development of the cerebral cortex. In particular, we are studying how the movement of the mitotic spindle apparatus and expression of fate determining molecules combine to allow for the switch between symmetrical and asymmetrical divisions during neocortical neurogenesis. We will study this process using time-lapse multiphoton microscopy, which enables long term visualization of the stem cells in their intact environment. Combining this imaging technology with overexpression of wild-type and dominant negative gene constructs via stem cell transfection will allow us to determine the molecular requirements of stem cell proliferation in a rapid and straightforward manner.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051852-03
Application #
7186693
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Owens, David F
Project Start
2005-02-15
Project End
2010-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$327,584
Indirect Cost
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
Tyler, William A; Haydar, Tarik F (2013) Multiplex genetic fate mapping reveals a novel route of neocortical neurogenesis, which is altered in the Ts65Dn mouse model of Down syndrome. J Neurosci 33:5106-19
Burke, Rebecca M; Norman, Timothy A; Haydar, Tarik F et al. (2013) BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 110:19567-72
Hevner, Robert F; Haydar, Tarik F (2012) The (not necessarily) convoluted role of basal radial glia in cortical neurogenesis. Cereb Cortex 22:465-8
Breunig, Joshua J; Haydar, Tarik F; Rakic, Pasko (2011) Neural stem cells: historical perspective and future prospects. Neuron 70:614-25
Stancik, Elizabeth K; Navarro-Quiroga, Ivan; Sellke, Robert et al. (2010) Heterogeneity in ventricular zone neural precursors contributes to neuronal fate diversity in the postnatal neocortex. J Neurosci 30:7028-36
Tyler, William A; Haydar, Tarik F (2010) A new contribution to brain convolution: progenitor cell logistics during cortex development. Nat Neurosci 13:656-7
Loulier, Karine; Lathia, Justin D; Marthiens, Veronique et al. (2009) beta1 integrin maintains integrity of the embryonic neocortical stem cell niche. PLoS Biol 7:e1000176
Gadea, Ana; Aguirre, Adan; Haydar, Tarik F et al. (2009) Endothelin-1 regulates oligodendrocyte development. J Neurosci 29:10047-62
Corbin, Joshua G; Gaiano, Nicholas; Juliano, Sharon L et al. (2008) Regulation of neural progenitor cell development in the nervous system. J Neurochem 106:2272-87
Corbin, Joshua G; Haydar, Tarik F (2007) Quantum dots for neuroscience research: new tools for old problems? Nanomedicine (Lond) 2:579-81

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