| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
In our previous study, we reported that mice deficient for the rae28 gene, a mouse homologue of the Drosophila polycomb group (PcG) of genes, show anomalies including defects of the neural crest derived tissues, in addition to the posterior transformation of skeletons (Takihara et al., Development, 124, 3673-82, 1997). In the present study, we examined the molecular mechanisms underlying the abnormal cardiac development in the rae28-deficient embryos, and found that the expression of a homeobox gene Nkx2.5 is markedly reduced in the heart of embryos from embryonic day 9.5 (E9.5), while it is normally initiated. We also examined the expression of 34 Hox genes in paraxial mesoderm, hindbrain and pharyngeal arches of the rae28-deficient embryos by in situ hybridization. Except for Hoxb3 and Hoxb4, the expression patterns of all 12 Hox genes expressed in the hindbrains and pharyngeal arches of the wild-type embryos are not affected. Ectopic expression of Hoxb3 was observed in the hindbrain from E10.5, and in the pharyngeal arch, from E9.5. These results and the expression patterns of a neural crest marker, p75, suggest that the neural crest cells begin to ectopically express Hoxb3 after leaving the hindbrain. Interestingly, the anterior boundary of ectopic expression in the hindbrain extends gradually in the rostral direction during development. We found that the rae28 gene product forms complexes with the products of other PcG genes, such as M33, bmil and mel18. These results indicate that the PcG complexes present in the rae28-deficient mice cannot stably fix and maintain Hoxb3 expression patterns.
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