title: BMPs regulate msx gene expression in the dorsal neuroectoderm of Drosophila and vertebrates by distinct mechanisms.
abstract: In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.
authors.affiliation: Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Francisco F
authors.initials: FF
authors.lastname: Esteves
authors.affiliation: Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM) Albert-Ludwigs-University of Freiburg, Freiburg, Germany; Research Training Program GRK 1104, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Springhorn
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Erika
authors.initials: E
authors.lastname: Kague
authors.affiliation: Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Erika
authors.initials: E
authors.lastname: Taylor
authors.affiliation: Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: George
authors.initials: G
authors.lastname: Pyrowolakis
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shannon
authors.initials: S
authors.lastname: Fisher
authors.affiliation: Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Ethan
authors.initials: E
authors.lastname: Bier
mesh_terms: D000818:Animals; D001665:Binding Sites; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D000090322:Homeobox Protein Nkx-2.2; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D037941:Silencer Elements, Transcriptional; D014714:Vertebrates / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D000090322:Homeobox Protein Nkx-2.2; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish