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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurogenesis and Cell Fate Study Section (NCF)
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Panchision, David M
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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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; Fernandez, 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
Siegenthaler, Julie A; Pleasure, Samuel J (2011) We have got you 'covered': how the meninges control brain development. Curr Opin Genet Dev 21:249-55
Wang, Yanling; Li, Guangnan; Stanco, Amelia et al. (2011) CXCR4 and CXCR7 have distinct functions in regulating interneuron migration. Neuron 69:61-76
Gu, Xiaochun; Yan, Yan; Li, Hanlin et al. (2009) Characterization of the Frizzled10-CreER transgenic mouse: an inducible Cre line for the study of Cajal-Retzius cell development. Genesis 47:210-6
Hoch, Renee V; Rubenstein, John L R; Pleasure, Sam (2009) Genes and signaling events that establish regional patterning of the mammalian forebrain. Semin Cell Dev Biol 20:378-86
Li, Guangnan; Kataoka, Hiroshi; Coughlin, Shaun R et al. (2009) Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling. Development 136:327-35
Gu, Xiaochun; He, Dongyang; Li, Yiping et al. (2008) Generation of Frizzled10-Cre transgenic mouse line: a useful tool for the study of dorsal telencephalic development. Genesis 46:523-9

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