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Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci

Department of Chemical Engineering and The Helen Wills Neuroscience Institute, 201 Gilman Hall, University of California, Berkeley, California 94720-1462, USA.
Nature Neuroscience (Impact Factor: 14.98). 02/2003; 6(1):21-7. DOI: 10.1038/nn983
Source: PubMed

ABSTRACT Neural stem cells exist in the developing and adult nervous systems of all mammals, but the basic mechanisms that control their behavior are not yet well understood. Here, we investigated the role of Sonic hedgehog (Shh), a factor vital for neural development, in regulating adult hippocampal neural stem cells. We found high expression of the Shh receptor Patched in both the adult rat hippocampus and neural progenitor cells isolated from this region. In addition, Shh elicited a strong, dose-dependent proliferative response in progenitors in vitro. Furthermore, adeno-associated viral vector delivery of shh cDNA to the hippocampus elicited a 3.3-fold increase in cell proliferation. Finally, the pharmacological inhibitor of Shh signaling cyclopamine reduced hippocampal neural progenitor proliferation in vivo. This work identifies Shh as a regulator of adult hippocampal neural stem cells.

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    • "Exogenous Shh protein has also been shown to increase the production of multipotent, self-renewing neurospheres cultured from adult stem cells of the V-SVZ or SGZ, suggesting that signaling through this pathway affects stem cell proliferation, the balance between self-renewal and differentiation, or both [11] [63]. In contrast to the localization of Shh transcript and subsequent analyses using knock-in mouse alleles to label cell bodies, Shh protein has been detected in the dentate gyrus, cerebrospinal fluid, and the neuropil surrounding the ventral V-SVZ [63] [64]. However, the mechanisms through which Shh protein is secreted and reaches these regions remain to be elucidated. "
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    Seminars in Cell and Developmental Biology 09/2014; 33. DOI:10.1016/j.semcdb.2014.05.008 · 5.97 Impact Factor
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    • "Pharmacological inhibition of SHH signaling with cyclopamine also reduced the cell proliferation in the DG (Lai et al., 2003). Conversely, elevated hedgehog signaling produced increased cell proliferation in the DG, further confirming the mitogenic effects of SHH in vivo (Lai et al., 2003; Machold et al., 2003; Han et al., 2008). Interestingly, it appears that the SHH signaling required for DG proliferation is mediated via primary cilia. "
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    ABSTRACT: Granule neurons in the hippocampal dentate gyrus (DG) receive their primary inputs from the cortex and are known to be continuously generated throughout adult life. Ongoing integration of newborn neurons into the existing hippocampal neural circuitry provides enhanced neuroplasticity, which plays a crucial role in learning and memory; deficits in this process have been associated with cognitive decline under neuropathological conditions. In this Primer, we summarize the developmental principles that regulate the process of DG neurogenesis and discuss recent advances in harnessing these developmental cues to generate DG granule neurons from human pluripotent stem cells.
    Development 06/2014; 141(12):2366-75. DOI:10.1242/dev.096776 · 6.27 Impact Factor
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    • " factor beta - 1 is a heparin binding molecule ( McCaffrey et al . , 1992 ) that inhibit cell proliferation in the SVZ ( Wachs et al . , 2006 ) . In the other hand , Sonic hedgehog and heparin - binding epidermal growth factor are heparin binding molecules ( Chang et al . , 2011 ; Jin et al . , 2002 ) that stimulate cell proliferation in the SVZ ( Lai et al . , 2003 ; Jin et al . , 2002 ) ."
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