RT Journal Article
SR Electronic
T1 High levels of expression of the tumor suppressor gene APC during development of the rat central nervous system
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3059
OP 3071
DO 10.1523/JNEUROSCI.14-05-03059.1994
VO 14
IS 5
A1 RV Bhat
A1 JM Baraban
A1 RC Johnson
A1 BA Eipper
A1 RE Mains
YR 1994
UL http://www.jneurosci.org/content/14/5/3059.abstract
AB 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.