In primates including human, the generation of neurons occurs during development while the brain is growing. This imposes natural constraints on adult brain repair. Recently it was discovered that unlike primates, adult birds continue to generate new neurons throughout their forebrain. These cells originate from discrete regions in the ventricular zone (VZ). The young neurons then adopt an elongated shape as they separate from the VZ at 20-30 um/hr using radial glial fibers as guides. Differentiation into mature neurons occurs 20-40 days later up to 6 mm away from their site of birth. The present proposal takes advantage of this model system for neurogenesis to study the origins of the new neurons. The PI's objectives are: 1) Identify the stem cells in the VZ of adult birds that give rise to the young migrating neurons. 2) Develop monoclonal antibodies (Mab) as markers to these precursor cells and to the young migrating neurons.3) Test the significance of radial glial proliferation in the adult avian brain.4) Understand the local movement of precursor cells within the VZ in relation to their proliferation dynamics. 5) Develops a new experimental approach to study neuronal migration. Electron microscopy (EM) and immunocytochemistry combined with [3H]-thymidine autoradiography will be used to identify the precursor cells in the VZ that give rise to neurons.Disaggregated VZ cells and transplantation and culture techniques are combined to study the early events leading to neurogenesis. The cells that give rise to the new neurons, their site of origin and their proliferation time table will be determined. The migration of live young neurons as they separate from the VZ will be followed under the microscope in brain slices.Their behavior on different terrains will reveal orientation cues used during migration. Cells born in the adult avian VZ only give rise to neurons. Neurogenesis occurs against a distinct background of unchanging adult brain parenchyma. Establishing the cellular prerequisites for adult neurogenesis and the mechanism that brings neurons to sites where needed in an adult brain could have a significant impact on approaches to brain repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS028478-04
Application #
3478027
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
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
Tate, Matthew C; Lindquist, Robert A; Nguyen, Thuhien et al. (2015) Postnatal growth of the human pons: a morphometric and immunohistochemical analysis. J Comp Neurol 523:449-62
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-Pérez, 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
Merkle, Florian T; Fuentealba, Luis C; Sanders, Timothy A et al. (2014) Adult neural stem cells in distinct microdomains generate previously unknown interneuron types. Nat Neurosci 17:207-14
Ohata, Shinya; Nakatani, Jin; Herranz-Pérez, Vicente et al. (2014) Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus. Neuron 83:558-71
Álvarez-Buylla, Arturo; Ihrie, Rebecca A (2014) Sonic hedgehog signaling in the postnatal brain. Semin Cell Dev Biol 33:105-11
Tong, Cheuk Ka; Alvarez-Buylla, Arturo (2014) SnapShot: adult neurogenesis in the V-SVZ. Neuron 81:220-220.e1
Tong, Cheuk Ka; Han, Young-Goo; Shah, Jugal K et al. (2014) Primary cilia are required in a unique subpopulation of neural progenitors. Proc Natl Acad Sci U S A 111:12438-43

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