Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Research Abstract |
Group B1 Sox genes, encoding functionally analogous transcription factors, are thought to play important roles in multiple developmental processes. Among the six group B1 sox genes in zebrafish, sox2, sox3, sox19a and sox19b are initially expressed ubiquitously in the blastoderm. Their expression then becomes confined to the future ectoderm and finally to the future neuroectoderm. To investigate the functions of the group B1 sox genes during early development, we knocked down sox2, sox3, sox19a and soxl9b in zebrafish embryos individually or in various combinations. Single to triple knockdowns caused little to moderate morphological abnormalities, whereas quadruple knockdown embryos showed remarkably severe defects. These quadruple morphants showed partially dorsalized characteristics, as exemplified by the expansion of neural marker gene expression. Consistently, expression of bmp2b and bmp7 was reduced, suggesting the BMP-dependent dorsoventral patterning is impaired in the morphant. Additionally, the prechordal plate was posteriorly located and the notochord was shorter and wider. wnt11 and wnt5b were found to be decreased, which can account for the impairment of convergence and extension. Furthermore, although early neuroectoderm marker genes such as otx2 and zic2b were present, many genes involved in later processes of neural development, such as hesx1, krox20 and neurog1, were not, suggesting the group B1 sox genes are essential for neural cell fate determination.
|