Homeobox containing genes are a family of genes which have been shown in Drosophila to control pattern formation during development. These genes encode proteins which bind to DNA in a sequence specific manner. They contain a 180 bp conserved DNA domain called a homeobox. We have isolated several homeobox containing genes which are activated during early Xenopus development. We have determined their temporal and spatial expression pattern using Northern blot analysis and in situ hybridization. One of them, called PV.1 is the first transcription factor capable of mediating ventral mesoderm formation in Xenopus. PV.1 is inducible in uncommitted ectoderm by ventralizing growth factor BMP4. Like BMP4, PV.1 is expressed in the ventral marginal zone of gastrulating embryos. Over-expression of PV.1 yields ventralized tadpoles and rescues embryos partially dorsalized by LiCl treatment. In animal caps, PV.1 ventralizes induction by activin. All of these effects mimic those previously reported for BMP4. Finally, we have shown that PV.1 counteracts the dorsolaizing effects of dominant negative BMP4 receptor. These observations suggest that PV.1 is a likely target in the BMP4 signaling pathway regulating expression of genes necessary for the formation of ventral mesoderm. In addition to the homeobox gene family we have isolated new members of the Fork head gene family. The individual members of this family have a highly interesting expression pattern and at least some of them are oncogenes. The first Xenopus Fork head gene XFKH1 has many highly interesting features. It is activated at, or shortly after, the mid-blastula transition in the dorsal marginal bone of the embryo. In early gastrulae it is restricted to the organizer region. At later stages it is expressed in the notochord and neural organizer region. Furthermore, it is inducible by activin in isolated animal caps. Its expression pattern and inducibility by activin suggests that this gene has a critical importance for early pattern formation in Xenopus embryos. Its expression pattern and inducibility by activin suggests that this gene has a critical importance for early pattern formation in Xenopus embryos. We have shown that this gene belongs to a larger family of Fork head genes, which, like homeobox genes are involved in different aspects of pattern formation and cell differentiation. In addition, we have initiated similar research into pattern formation in Zebrafish embryos.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BM005001-03
Application #
5200770
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost