. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci. 2003 Jan;6(1):21-7. PubMed.

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  1. The intrinsic signals that regulate the extent of adult neurogenesis are incompletely understood. In neurodegenerative diseases such as Alzheimer’s disease, neuronal dysfunction and loss underlie cognitive impairment. Understanding and perhaps exploiting nature’s own mechanisms to generate new and functional neurons may represent a future therapeutic opportunity. In this interesting new paper Lai et al. demonstrate that Sonic hedgehog (Shh) can markedly stimulate neurogenesis. Unlike Shh, its receptor Patched (Ptc) is expressed in the hippocampus, thus raising the possibility that neuronal projections may control the delivery of Shh.

    Using combined in vitro and in vivo methods the investigators show that Ssh can increase the apparent rate of neurogenesis from precursor cells. Whereas lineage representation does not appear altered by Shh, the total number of surviving cells is increased. Whether these precursor-derived post-mitotic derivatives become functionally integrated into neuronal circuits is not yet known.

    Two most interesting observations warrant mention. Firstly, Shh gene transfer into dentate gyrus (DG) can trigger excessive neurogenesis. This may have relevance to a gene-therapeutic repopulation of the damaged and neuron-depleted hippocampal formation. Secondly, the afferent projections from basal forebrain to hippocampus regulate DG neurogenesis, perhaps in an Shh-dependent manner. The authors speculate that inhibitory septohippocampal GABAergic neurons release Shh in an activity-dependent manner. Such demonstration would catalyze the search for compounds that mimic this process as they might be used to control neurogenesis in an anatomically directed manner.

    View all comments by Howard Federoff

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