title: Tbx2/3 is an essential mediator within the Brachyury gene network during Ciona notochord development.
abstract: T-box genes are potent regulators of mesoderm development in many metazoans. In chordate embryos, the T-box transcription factor Brachyury (Bra) is required for specification and differentiation of the notochord. In some chordates, including the ascidian Ciona, members of the Tbx2 subfamily of T-box genes are also expressed in this tissue; however, their regulatory relationships with Bra and their contributions to the development of the notochord remain uncharacterized. We determined that the notochord expression of Ciona Tbx2/3 (Ci-Tbx2/3) requires Ci-Bra, and identified a Ci-Tbx2/3 notochord CRM that necessitates multiple Ci-Bra binding sites for its activity. Expression of mutant forms of Ci-Tbx2/3 in the developing notochord revealed a role for this transcription factor primarily in convergent extension. Through microarray screens, we uncovered numerous Ci-Tbx2/3 targets, some of which overlap with known Ci-Bra-downstream notochord genes. Among the Ci-Tbx2/3 notochord targets are evolutionarily conserved genes, including caspases, lineage-specific genes, such as Noto4, and newly identified genes, such as MLKL. This work sheds light on a large section of the notochord regulatory circuitry controlled by T-box factors, and reveals new components of the complement of genes required for the proper formation of this structure.
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, Box 60, New York, NY 10065, USA.
authors.forename: Diana S
authors.initials: DS
authors.lastname: José-Edwards
authors.forename: Izumi
authors.initials: I
authors.lastname: Oda-Ishii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nibu
authors.forename: Anna
authors.initials: A
authors.lastname: Di Gregorio
mesh_terms: D000818:Animals; D001665:Binding Sites; D019070:Cell Lineage; D002938:Ciona intestinalis / Q000196:embryology* / Q000502:physiology; D005326:Fetal Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D017403:In Situ Hybridization; D009154:Mutation; D009672:Notochord / Q000196:embryology* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D020825:T-Box Domain Proteins / Q000378:metabolism* / Q000502:physiology; D019076:Transgenes; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C097348:T-Box Domain Protein 2
keywords: Brachyury; Ciona; Notochord