title: BMP and retinoic acid regulate anterior-posterior patterning of the non-axial mesoderm across the dorsal-ventral axis.
abstract: Despite the fundamental importance of patterning along the dorsal-ventral (DV) and anterior-posterior (AP) axes during embryogenesis, uncertainty exists in the orientation of these axes for the mesoderm. Here we examine the origin and formation of the zebrafish kidney, a ventrolateral mesoderm derivative, and show that AP patterning of the non-axial mesoderm occurs across the classic gastrula stage DV axis while DV patterning aligns along the animal-vegetal pole. We find that BMP signalling acts early to establish broad anterior and posterior territories in the non-axial mesoderm while retinoic acid (RA) functions later, but also across the classic DV axis. Our data support a model in which RA on the dorsal side of the embryo induces anterior kidney fates while posterior kidney progenitors are protected ventrally by the RA-catabolizing enzyme Cyp26a1. This work clarifies our understanding of vertebrate axis orientation and establishes a new paradigm for how the kidney and other mesodermal derivatives arise during embryogenesis.
authors.affiliation: Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Naylor
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.|Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Lauren Brilli
authors.initials: LB
authors.lastname: Skvarca
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22903, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Thisse
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22903, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thisse
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.|Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hukriede
authors.affiliation: Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Davidson
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D004625:Embryo, Nonmammalian; D007668:Kidney / Q000196:embryology*; D008648:Mesoderm / Q000196:embryology*; D000072516:Retinoic Acid 4-Hydroxylase / Q000235:genetics*; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; D014212:Tretinoin; D000072516:Retinoic Acid 4-Hydroxylase; C000607085:cyp26a1 protein, zebrafish