1. Howard Hughes Medical Institute, Developmental Genetics Program, Skirball Institute of Biomolecular Medicine and Department of Cell Biology, and
2. Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
3. †Present address: Unit on Developmental Neurogenetics, Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Building 6B, Bethesda, Maryland 20892, USA

Correspondence to: Alexandra L. Joyner^1,2 Correspondence and requests for materials should be addressed to A.L.J. (Email: joyner@saturn.med.nyu.edu).

Abstract

Sonic hedgehog (Shh) has been implicated in the ongoing neurogenesis in postnatal rodent brains^{1, 2}. Here we adopted an in vivo genetic fate-mapping strategy, using Gli1 (GLI-Kruppel family member) as a sensitive readout of Shh activity, to systematically mark and follow the fate of Shh-responding cells in the adult mouse forebrain. We show that initially, only a small population of cells (including both quiescent neural stem cells and transit-amplifying cells) responds to Shh in regions undergoing neurogenesis. This population subsequently expands markedly to continuously provide new neurons in the forebrain. Our study of the behaviour of quiescent neural stem cells provides in vivo evidence that they can self-renew for over a year and generate multiple cell types. Furthermore, we show that the neural stem cell niches in the subventricular zone and dentate gyrus are established sequentially and not until late embryonic stages.

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