Induction of neurogenesis in the neocortex of adult mice

Rcjohnsen rcjohnsen at
Sun Jul 2 15:52:31 EST 2000

Induction of neurogenesis in the neocortex of adult mice
Division of Neuroscience, Children's Hospital, and
Department of Neurology and Program in Neuroscience, Harvard Medical School,
Enders 350, 320 Longwood Avenue, Boston, Massachusetts 02115 USA
* Present address: Center for Molecular Medicine and Therapeutics, Department
of Medical Genetics, University of British Columbia, Vancouver, British
Columbia V5Z 4H4 , Canada.

Correspondence and requests for materials should be addressed to J.D.M.
(e-mail: macklis at

Neurogenesis normally only occurs in limited areas of the adult mammalian
brain—the hippocampus1, olfactory bulb2-4 and epithelium5, and at low levels in
some regions of macaque cortex6. Here we show that endogenous neural precursors
can be induced in situ to differentiate into mature neurons, in regions of
adult mammalian neocortex that do not normally undergo any neurogenesis. This
differentiation occurs in a layer- and region-specific manner, and the neurons
can re-form appropriate corticothalamic connections. We induced synchronous
apoptotic degeneration7, 8 of corticothalamic neurons in layer VI of anterior
cortex of adult mice and examined the fates of dividing cells within cortex,
using markers for DNA replication (5-bromodeoxyuridine; BrdU) and progressive
neuronal differentiation. Newly made, BrdU-positive cells expressed NeuN, a
mature neuronal marker, in regions of cortex undergoing targeted neuronal death
and survived for at least 28 weeks. Subsets of BrdU+ precursors expressed
Doublecortin, a protein found exclusively in migrating neurons9, 10, and Hu, an
early neuronal marker11, 12. Retrograde labelling from thalamus demonstrated
that BrdU+ neurons can form long-distance corticothalamic connections. Our
results indicate that neuronal replacement therapies for neurodegenerative
disease and CNS injury may be possible through manipulation of endogenous
neural precursors in situ. 

Nature June 22, 00

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