title: Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries.
abstract: Pbx proteins are a family of TALE-class transcription factors that are well characterized as Hox co-factors acting to impart segmental identity to the hindbrain rhombomeres. However, no role for Pbx in establishing more anterior neural compartments has been demonstrated. Studies done in Drosophila show that Engrailed requires Exd (Pbx orthologue) for its biological activity. Here, we present evidence that zebrafish Pbx proteins cooperate with Engrailed to compartmentalize the midbrain by regulating the maintenance of the midbrain-hindbrain boundary (MHB) and the diencephalic-mesencephalic boundary (DMB). Embryos lacking Pbx function correctly initiate midbrain patterning, but fail to maintain eng2a, pax2a, fgf8, gbx2, and wnt1 expression at the MHB. Formation of the DMB is also defective as shown by a caudal expansion of diencephalic epha4a and pax6a expression into midbrain territory. These phenotypes are similar to the phenotype of an Engrailed loss-of-function embryo, supporting the hypothesis that Pbx and Engrailed act together on a common genetic pathway. Consistent with this model, we demonstrate that zebrafish Engrailed and Pbx interact in vitro and that this interaction is required for both the eng2a overexpression phenotype and Engrailed's role in patterning the MHB. Our data support a novel model of midbrain development in which Pbx and Engrailed proteins cooperatively pattern the mesencephalic region of the neural tube.
authors.affiliation: Department of Biological Sciences, CW405, Biological Sciences Building, University of Alberta, Edmonton AB, Canada T6G2E9.
authors.forename: Timothy
authors.initials: T
authors.lastname: Erickson
authors.forename: Steffen
authors.initials: S
authors.lastname: Scholpp
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.forename: Andrew Jan
authors.initials: AJ
authors.lastname: Waskiewicz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000196:embryology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D029961:Zebrafish Proteins; C079428:en2a protein, zebrafish; D000099266:Engrailed 2 Protein