Letter

Nature 451, 1004-1007 (21 February 2008) | doi:10.1038/nature06562; Received 7 September 2007; Accepted 10 January 2008; Published online 30 January 2008

A role for adult TLX-positive neural stem cells in learning and behaviour

Chun-Li Zhang1,2, Yuhua Zou2, Weimin He2,4, Fred H. Gage3 & Ronald M. Evans1,2

  1. Howard Hughes Medical Institute,
  2. Gene Expression Laboratory, and,
  3. Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
  4. Present address: The Institute of Biosciences and Technology, 2121 W. Holcombe Boulevard, Houston, Texas 77030, USA.

Correspondence to: Fred H. Gage3Ronald M. Evans1,2 Correspondence and requests for materials should be addressed to R.M.E. (Email: evans@salk.edu) or F.H.G. (Email: gage@salk.edu).

Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress1. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network2, 3, 4, 5, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions6. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells7. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

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