How do the cells of the gastrula move to form an embryo? The long term objective of the proposed work is to understand the genetic and biomechanical basis for gastrulation in a model vertebrate, the zebrafish. The zebrafish processes unique optical and genetic properties that make it ideal for these studies. Moreover, the recent isolation of zebrafish mutants that are deficient in cell motility have identified many of the genes necessary for cell motility. The gene half baked (hab) is essential for the process of epiboly, the vegetalwards spreading of the blastoderm to cover the large yolk cell. This process is the first morphogenetic movement of the zebrafish gastrula and is similar in principle to the pregastrulation spreading movements in Xenopus and mouse. Mutations in hab arrest epiboly. Furthermore, hab possesses a maternal- zygotic dominant effect phenotype, an unique genetic interaction, indicating that hab is necessary both maternally and zygotically. Understanding the early role of hab will be crucial for our understanding of cell motility in the early embryo and the zygotic and maternal controls on this motility. The specific objectives of this proposal are aimed at understanding the zygotic and maternal roles of hab in the zebrafish gastrula, and at establishing the molecular nature of hab. The gene hab is necessary for the blastoderm to participate in epiboly. The generally accepted hypothesis for teleost epiboly is that the yolk cell tows the blastoderm toward the vegetal pole. Several lines of evidence argue that hab may acting in the blastoderm, challenging this simple towing hypothesis.
The specific aims of this proposal are: l) to identify the molecular nature of hab, 2) to delineate the maternal affect phenotype of hab by creating germline chimerae, 3) to complete the cellular characterization of hab, testing the towing hypothesis of epiboly by locating the site of action of hab using cell transplantation, 4) to assay the interactions between hab and the gene spadetail, a gene that also necessary for cell motility of the deep cells of the blastoderm. Achieving these objectives will lead to an understanding of hab gene function as well as a detailed understanding of the morphogenetic movement of epiboly. Such an understanding will have broad application, not only to the study of teleost embryology but to birth defects in humans and the spreading of cells in metastasizing cancers. Furthermore, this work will lead to a fresh new view of cell motility in vertebrate embryology.
| Warga, Rachel M; Kane, Donald A (2007) A role for N-cadherin in mesodermal morphogenesis during gastrulation. Dev Biol 310:211-25 |
| McFarland, Karen N; Warga, Rachel M; Kane, Donald A (2005) Genetic locus half baked is necessary for morphogenesis of the ectoderm. Dev Dyn 233:390-406 |
| Warga, Rachel M; Kane, Donald A (2003) One-eyed pinhead regulates cell motility independent of Squint/Cyclops signaling. Dev Biol 261:391-411 |
| Dougan, Scott T; Warga, Rachel M; Kane, Donald A et al. (2003) The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm. Development 130:1837-51 |
