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Journal of Neuroscience, Vol 14, 3059-3071, Copyright © 1994 by Society for Neuroscience
High levels of expression of the tumor suppressor gene APC during development of the rat central nervous system
RV Bhat, JM Baraban, RC Johnson, BA Eipper and RE Mains
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
The adenomatous polyposis coli (APC) gene is a tumor suppressor gene that
is mutated in human familial adenomatous polyposis, an autosomal dominant
condition with predisposition to colorectal carcinoma and brain tumors.
Although tumor suppressor genes appear to play a general role in regulating
cellular proliferation, the normal biological function of the APC gene
product is unknown. In the present study, we cloned fragments of the rat
homolog of the APC gene and examined its tissue distribution by Northern
blot analysis. These studies demonstrated particularly high levels of APC
mRNA in brain. To gain clues to the role of the APC gene in brain function,
we examined the neuroanatomical distribution of APC mRNA using in situ
hybridization. In the adult, prominent expression of APC mRNA was observed
in the olfactory bulb, hippocampus, and cerebellum, with low levels of
hybridization in other regions of adult rat brain. In contrast, during
embryonic and early postnatal development (1-2 weeks), high levels of APC
expression were found throughout the brain and then decreased to adult
levels by 6 weeks after birth, except in the olfactory bulb where the high
levels of APC mRNA found in development persist in the adult. During
development of cortex, cerebellum, and retina, APC mRNA expression was
particularly prominent in layers containing newly formed postmitotic
neurons, with lower levels observed in the proliferative zones where
neurogenesis occurs. The high levels of APC expression from early
neurogenesis until late stages of neuronal maturation suggest that APC may
contribute to suppressing neuronal proliferation during this period of
intense growth.
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