IPP isomerase, an enzyme of mevalonate pathway, is preferentially expressed in postnatal cortical neurons and induced after nerve transection.
To understand the molecular mechanisms underlying the developmental processes of the cerebral cortex, we screened genes whose mRNA expression was up-regulated in neonatal in the rat cortex to a greater extent than in adult by differential display and obtained five genes. Among these genes, we focused on pyrophosphate (isopentenyl diphosphate, dimethylallyl diphosphate: IPP) isomerase gene, the product of which is known as an enzyme of the mevalonate pathway. Rat IPP isomerase was recently cloned and the gene expression was shown to be dependent on the activation of the mevalonate pathway. Its expression and roles in the brain, however, have not been investigated hitherto. In the present study, Northern blots and in situ hybridization analysis showed that at embryonic stage weak signals for IPP mRNA were diffusely detected in the CNS, and the signal in the cortex became intense at postnatal day 1 and maximized in almost all neurons of all layers at postnatal day 7 with a subsequent reduction. At 8 weeks, the expression of IPP isomerase mRNA in neurons decreased, while it was detected in the oligodendrocytes in the regions containing abundant nerve fibers. These findings suggested that IPP isomerase contributes to postnatal neuronal maturation and myelination. We also demonstrated that IPP isomerase mRNA is induced after nerve axotomy, which suggests a relationship between neuronal regeneration and IPP isomerase. Taken together, these results suggest that elevation of IPP isomerase mRNA levels in neurons contributes to construction of nerve fibers both during the postnatal period in the cortex and their regeneration.
Morihara
T
T
Department of Neuropsychiatry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. morihara@anat2.med.osaka-u.ac.jp
Tanabe
K
K
Yoneda
T
T
Tanaka
T
T
Kudo
T
T
Gomi
F
F
Kiyama
H
H
Imaizumi
K
K
Tohyama
M
M
Takeda
M
M
D000818:Animals; D019771:Axotomy; D001483:Base Sequence; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000235:genetics; D019748:Carbon-Carbon Double Bond Isomerases / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D003337:Corpus Callosum / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D018076:DNA, Complementary; D003711:Demyelinating Diseases / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D015723:Gene Library; D045782:Hemiterpenes; D007002:Hypoglossal Nerve / Q000201:enzymology* / Q000601:surgery; D008798:Mevalonic Acid / Q000378:metabolism*; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics; D009474:Neurons / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D018076:DNA, Complementary; D045782:Hemiterpenes; D012333:RNA, Messenger; D019748:Carbon-Carbon Double Bond Isomerases; C021453:isopentenyldiphosphate delta-isomerase; D008798:Mevalonic Acid