title: Pbx4 is Required for the Temporal Onset of Zebrafish Myocardial Differentiation.
abstract: Proper control of the temporal onset of cellular differentiation is critical for regulating cell lineage decisions and morphogenesis during development. Pbx homeodomain transcription factors have emerged as important regulators of cellular differentiation. We previously showed, by using antisense morpholino knockdown, that Pbx factors are needed for the timely activation of myocardial differentiation in zebrafish. In order to gain further insight into the roles of Pbx factors in heart development, we show here that zebrafishpbx4mutant embryos exhibit delayed onset of myocardial differentiation, such as delayed activation oftnnt2aexpression in early cardiomyocytes in the anterior lateral plate mesoderm. We also observe delayed myocardial morphogenesis and dysmorphic patterning of the ventricle and atrium, consistent with our previous Pbx knock-down studies. In addition, we find thatpbx4mutant larvae have aberrant outflow tracts and defective expression of the proepicardial markertbx18. Finally, we present evidence for Pbx expression in cardiomyocyte precursors as well as heterogeneous Pbx expression among the pan-cytokeratin-expressing proepicardial cells near the developing ventricle. In summary, our data show that Pbx4 is required for the proper temporal activation of myocardial differentiation and establish a basis for studying additional roles of Pbx factors in heart development.
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kao
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
authors.forename: Joel G
authors.initials: JG
authors.lastname: Rurik
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
authors.forename: Gist H
authors.initials: GH
authors.lastname: Farr
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
authors.forename: Xiu Rong
authors.initials: XR
authors.lastname: Dong
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA; Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Majesky
authors.affiliation: Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA; Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Maves
keywords: cardiomyocyte; differentiation; myocardial morphogenesis; outflow tract; pbx4; proepicardium; zebrafish