The subventricular zone (SVZ) in juvenile and adult mammalian brains, including primates, contain a population of rapidly proliferative cells. New neurons and glia can be derived from these proliferating SVZ precursors in adult mice. Adult SVZ cells can also be grown in vitro with EGF or bFGF and these cells retain the potential to form neurons and glia in vitro. In rodents, SVZ cells migrate several mm to the olfactory bulb where they differentiate into neurons. These SVZ cells migrate associated with each other, forming chains of neuronal precursors (chain migration), faithfully reaching the olfactory bulb without raidal glia or axons for guidance. An extensive network for chain migration exits in the SVZ of adult mice suggesting that an unprecedented traffic of neuronal precursors exist in the adult mammalian brain. The goal is to determine the potential of the adult SVZ to generate new neurons for brain repair. To this end, the following question will be addressed. 1) Is the olfactory bulb required for the migration and proliferation of SVZ precursors? 2) Can SVZ precursors generate new neurons after transplantation into different regions of the adult brain? 3) Do chains of neuronal precursors exist in the brain of other adult vertebrates including primates and humans? 4) Which of the 5 cell types that the investigator has recently characterized in the SVZ of adult mice grow with EGF or bFGF in vitro? 5) Can SVZ precursors, either isolated directly from the brain or cultured in vitro with growth factors integrate and generate different neuronal types following transfer into the embryonic brain?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD032116-06
Application #
2889126
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Nitkin, Ralph M
Project Start
1994-09-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Obernier, Kirsten; Cebrian-Silla, Arantxa; Thomson, Matthew et al. (2018) Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation. Cell Stem Cell 22:221-234.e8
Yang, Nan; Chanda, Soham; Marro, Samuele et al. (2017) Generation of pure GABAergic neurons by transcription factor programming. Nat Methods 14:621-628
Spatazza, Julien; Mancia Leon, Walter R; Alvarez-Buylla, Arturo (2017) Transplantation of GABAergic interneurons for cell-based therapy. Prog Brain Res 231:57-85
Ohata, Shinya; Alvarez-Buylla, Arturo (2016) Planar Organization of Multiciliated Ependymal (E1) Cells in the Brain Ventricular Epithelium. Trends Neurosci 39:543-551
Paredes, Mercedes F; Sorrells, Shawn F; Garcia-Verdugo, Jose M et al. (2016) Brain size and limits to adult neurogenesis. J Comp Neurol 524:646-64
Paredes, Mercedes F; James, David; Gil-Perotin, Sara et al. (2016) Extensive migration of young neurons into the infant human frontal lobe. Science 354:
Harwell, Corey C; Fuentealba, Luis C; Gonzalez-Cerrillo, Adrian et al. (2015) Wide Dispersion and Diversity of Clonally Related Inhibitory Interneurons. Neuron 87:999-1007
Tong, Cheuk Ka; Fuentealba, Luis C; Shah, Jugal K et al. (2015) A Dorsal SHH-Dependent Domain in the V-SVZ Produces Large Numbers of Oligodendroglial Lineage Cells in the Postnatal Brain. Stem Cell Reports 5:461-70
Fuentealba, Luis C; Rompani, Santiago B; Parraguez, Jose I et al. (2015) Embryonic Origin of Postnatal Neural Stem Cells. Cell 161:1644-55
Ohata, Shinya; Herranz-PĂ©rez, Vicente; Nakatani, Jin et al. (2015) Mechanosensory Genes Pkd1 and Pkd2 Contribute to the Planar Polarization of Brain Ventricular Epithelium. J Neurosci 35:11153-68

Showing the most recent 10 out of 68 publications