Genetic Cascade Underlying the Formation of the Notochord in Urochordate Embryos

Nori Satoh
Department of Zoology, Faculty of Science, Kyoto University, Kyoto, Japan

Number of Words: 354
Number of References: 2 
Number of Figures: 0 
Number of Tables:  0

Running header text: Notochord in Urochordate Embryos

Multicellular animals are sub-grouped in general into those with backbone (vertebrates) and those without backbone (invertebrates).  However, the primordial organ of vertebrates, namely the notochord, is also possessed by the urochordates (or tunicates) and cephalochordates.  Vertebrates are thus a subgroup of the Phylum Chordata, together with urochordates (animals with the notochord in the tail) and cephalochordates (animals with the notochord extending to the tip of the head) (Satoh 2003).  These three groups also share a dorsal, hollow neural tube (or nerve chord), gill slits, an endostyle and other features, and evolved from a common ancestor at least 520 million years ago.
The notochord is a defining property of all chordates.  Brachyury encodes a sequence-specific transcription activator and plays a key role in the differentiation of the notochord in a broad spectrum of chordates, including ascidians, Amphioxus, fish, frogs, chickens and mice.  We show here that the major upstream genetic cascade leading to notochord cell specification is maternal beta-catenin, FoxD at the 16-cell stage, ZicL at the 32-cell stage and Brachyury at the 64-cell stage.  In addition, we have explored the downstream cascade for Brachyury expression.  We could lead Brachyury expression ectopically in endodermal cells in thousands of embryos.  Using this system, we have already isolated more than 20 Brachyury-downstream genes, which re-expressed in Ciona (Satoh et al. 2003) embryos at neurula and tailbud-embryo stages.  An examination of the function of the Brachyury-downstream notochord genes demonstrated that these genes are involved in convergent-extension movements required for the notochord-rod formation at the midline of the tailbud embryo.
	Brachyury is conserved in non-chordate invertebrates, and the gene of hemichordates and echinoderms is expressed during development in the archenteron invagination region and mouth invagination region.  Brachyury of both hemichordates and echinoderms is able to form notochord cells when the gene is mis-expressed in ascidians, namely the molecular function to form notochord is conserved in non-chordate deuterostomes.

References
Satoh, N.  2003.  The ascidian tadpole larva:  Comparative molecular development and genomics.  Nature Review of Genetics, 4, 285-295.

Satoh, N., Satou, Y., Davidson, B. & Levine, M.  2003.  Ciona intestinalis:  an emerging model for whole-genome analyses.  Trends in Genetics, 19, 376-381.