The discovery of neural stem/progenitor cells and persistent neurogenesis in restricted brain regions has ignited an unprecedented interest in developing cell restoration therapies, which are designed to repair the malfunctional cells and/or replace the defunct cells in the nervous system in the case of diseases or injuries. Conceivably, we can achieve these either by coaching endogenous stem/progenitor cells for self-repair/self-replenishment, or by transplanting exogenous stem/progenitor cells to differentiate in a defined manner to restore defective or lost cells. However, the successful utilization of neural stem/progenitor cells in either case is contingent on their ability to behave and function in vivo n a biologically meaningful way without causing adverse effects. Many studies in recent years indicate that the fate and behavior of stem/progenitor cells are governed by the local microenvironment, termed the """"""""niche"""""""". Therefore, a better understanding of the interactions between the stem/progenitor cells and their niche is a critical step toward effective stem cell therapies. We hope to elucidate the molecular cues mediating interactions between stem/progenitor cells and their niche during development and to encourage use of this knowledge to develop novel approaches for treating neural injuries and neurodegenerative diseases through the following two aims.
Aim #1 : Examine the contribution of the ventral hippocampal ventricular zone to the production of subgranular NSCs throughout the hippocampus.
Aim #2 : Characterize the roles of various sources of Shh in SGZ development.

Public Health Relevance

The dentate gyrus has the capacity to produce new neurons in adults. This capacity is related to learning and memory in the dentate, and diseases such as schizophrenia, depression, epilepsy and Alzheimer's are associated with defects in neuron production. This proposal studies the basic mechanisms governing the development of the dentate and its specialized ability to continue to produce new neurons throughout life.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH077694-06A1
Application #
8371088
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Panchision, David M
Project Start
2006-07-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
6
Fiscal Year
2012
Total Cost
$386,250
Indirect Cost
$136,250
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Choe, Youngshik; Huynh, Trung; Pleasure, Samuel J (2015) Epithelial cells supply Sonic Hedgehog to the perinatal dentate gyrus via transport by platelets. Elife 4:
Choe, Youngshik; Pleasure, Samuel J; Mira, Helena (2015) Control of Adult Neurogenesis by Short-Range Morphogenic-Signaling Molecules. Cold Spring Harb Perspect Biol 8:a018887
Yabut, Odessa R; Fernandez, Gloria; Huynh, Trung et al. (2015) Suppressor of Fused Is Critical for Maintenance of Neuronal Progenitor Identity during Corticogenesis. Cell Rep 12:2021-34
Berberoglu, Michael A; Dong, Zhiqiang; Li, Guangnan et al. (2014) Heterogeneously expressed fezf2 patterns gradient Notch activity in balancing the quiescence, proliferation, and differentiation of adult neural stem cells. J Neurosci 34:13911-23
Choe, Youngshik; Kozlova, Anastasiia; Graf, Daniel et al. (2013) Bone morphogenic protein signaling is a major determinant of dentate development. J Neurosci 33:6766-75
Li, Guangnan; Fang, Li; Fernández, Gloria et al. (2013) The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus. Neuron 78:658-72
Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J (2012) A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation. Neuron 73:698-712
Choe, Youngshik; Pleasure, Samuel J (2012) The GAP between axon pruning and repulsion. Dev Cell 23:3-4
Ultanir, Sila K; Hertz, Nicholas T; Li, Guangnan et al. (2012) Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 Uncovers their roles in dendrite arborization and spine development. Neuron 73:1127-42
Harrison-Uy, Susan J; Pleasure, Samuel J (2012) Wnt signaling and forebrain development. Cold Spring Harb Perspect Biol 4:a008094

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