|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
The homozygote of Polydactyly mouse (Pdn/Pdn) shows preaxial polydactyly and arhinecephaly, and its responsible gene has been considered to be Gli3 on chromosome 13A2-3. Greig cephalopolysyndactyly syndrome (GCPS) shows peculiar facial feature including broad nasal root and telecanthus, and polydactyly arid syndactyly both In the foot and hand. Its responsible gene is GLI3 on chromosome 7p13. From the high homology between Gli3 and GLI3 genes, the similarity of phenotypes, and synteny of their chromosomes, Pdn/Pdn was considered to be a mouse homologue of human GCPS.It was thought that developmental mechanisms in Pdn/Pdn mouse can be extrapolated to the developmental mechanism of GCPS.In this study, developmental mechanisms of Pdn/Pdn mouse was investigated especially in the olfactory nerve, olfactory bulb formation and trigeminal nerve.
1) Olfactory nerve fiber projection were investigated by DiI.The olfactory nerve fibers attached and invaded into the telencephalon on day 12 of gestat
ion, and anterior part of telencephalon protruded to form the olfactory bulb primodium on day 13 of gestation in the normal mouse embryos. While, the olfactory nerve fibers did not attach and invade the telencephalon during any developmental stages in Pdn/Pdn mouse embryos. From thIs phenomenon, it was suggested that the protrusion of the olfactory bulb was not induced by the non-attachment of the olfactory nerve fibers to the telencephalon.
2) Olfactory nerve fibers did not invade the central nervous systems, and olfactory nerve fibers formed a tangled mass under the forebrain or cerebral hemisphere in the meninges in Pdn/Pdn embryos. In the electron microscopic observations, there were no synaps in the tangle of the olfactory nerve on the cribriform plate in Pdn/Pdn newborns.
3) Olfactory bulb and accessory olfactory bulb were not formed in Pdn/Pdn. But, primordial mitral/tufted cells which construct the olafactory bulb were detected by the immunohistochemical staining using anti-OCAM (olfactory cell adhesion molecule) antibody in Pdn/Pdn. That means, anterior part of telencephalon has a destine to differentiate to be the mitral/tufted cells without olfactory nerve innervation. Then, protrusion of the olfactory bulb from the telencephalon is induced by the innervation of the olfactory nerve fibers till day 12 of gestation. Thus, it was suggested that the mechanisms to form the olfactory bulb have 2 steps.
4) Pdn/Pdn die soon after birth without sucking their mother's milk. it was considered that mouse newborns search their mother's nipples using either their whisker or olfaction. Whisker is innervated by the trigeminal nerve. Trigeminal nerve fibers in Pdn/Pdn mouse embryos were investigated by the immunohistochemical staining using anti-neurofilament antibody. Trigeminal ganglion, outgrowth of trigeminla nerve fiber bundles, and its innervation of the whisker follicles were normal in Pdn/Pdn. Pdn/Pdn has abnormalities in the olfactory system as mentioned above, so suckling dysfuction in Pdn/Pdn was considered to be caused by the dysfunction of the olfactory system. Less