| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The dorsoventral specification of vertebrate CNS has been examined using zebrafish embryos.
1. The floor plate is located at the ventral midline of the neural tube in vertebrates. The floor-plate development is severely impaired in zebrafish one-eyed pinhead (oep) mutants. To understand the cell behavior and cell-cell interaction during floor plate development, we examined the distribution and gene expression of wild-type and oep mutant cells in genetic mosaics. The results indicate that oep mutant cells adopt only a notochord fate in a wild-type environment. In oep hosts that received wild-type cells, wild-type donor cells frequently contributed to part of the floor-plate region and expressed floor-plate markers. Careful examination of serial sections revealed that a mutant neural cell, when located next to the wild-type cells, inhibited floor-plate differentiation of the adjacent wild-type cells. This repressive interaction may play an important role in restricting the floor-plate region into the ventral-most midline by antagonizing homeogenetic signals from the floor-plate cells.
2. Telencephalon, which gives rise to the cerebral hemisphere, develops from the dorso-anterior part of the forebrain. Recent studies with mice have shown that Fgf8 expressed in the anterior neural ridge functions as a local signaling molecule in the specification of the telencephalic region. To explore the role of Fgf signaling in zebrafish developing CNS, we have examined the spatial pattern of activation of the extracellular signal regulated kinase , one of the downstream mediator of FGF receptor, and show that it closely resembles the expression of fgf3 in the anterior neural region. We then injected the dominant-negative form of Ras or the inhibitor of the FGF receptor into zebrafish embryos and examined defects in anterior neural region. The results obtained suggest that Fgf signaling, mediated by Ras/MAPK cascade, is required for the establishment of the ventral telencephalon.
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