title: An early Fgf signal required for gene expression in the zebrafish hindbrain primordium.
abstract: We have explored the role of fibroblast growth factor (Fgf) signaling in regulating gene expression in the early zebrafish hindbrain primordium. We demonstrate that a dominant negative Fgf receptor (FgfR) construct disrupts gene expression along the entire rostrocaudal axis of the hindbrain primordium and, using an FgfR antagonist, we find that this Fgf signal is required at early gastrula stages. This effect cannot be mimicked by morpholino antisense oligos to Fgf3, Fgf8 or Fgf24--three Fgf family members known to be secreted from signaling centers at the midbrain-hindbrain boundary (MHB), in rhombomere 4 and in caudal mesoderm at gastrula stages. We propose that an Fgf signal is required in the early gastrula to initiate hindbrain gene expression and that this is distinct from the later roles of Fgfs in patterning the hindbrain during late gastrula/early segmentation stages. We also find that blocking either retinoic acid (RA) or Fgf signaling disrupts hindbrain gene expression at gastrula stages, suggesting that both pathways are essential at this stage. However, both pathways must be blocked simultaneously to disrupt hindbrain gene expression at segmentation stages, indicating that these signaling pathways become redundant at later stages. Furthermore, exogenous application of RA or Fgf alone is sufficient to induce hindbrain genes in gastrula stage tissues, suggesting that the two-signal requirement can be overcome under some conditions. Our results demonstrate an early role for Fgf signaling and reveal a dynamic relationship between the RA and Fgf signaling pathways during hindbrain development.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, and Program in Neuroscience, University of Massachusetts Medical School, 364 Plantation Street-LRB 822, Worcester, MA 01605, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Roy
authors.forename: Charles G
authors.initials: CG
authors.lastname: Sagerström
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004625:Embryo, Nonmammalian; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000502:physiology*; D005775:Gastrula / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D008845:Microinjections / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020897:Organizers, Embryonic / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012249:Rhombencephalon / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D011500:Protein Synthesis Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D018168:Receptors, Retinoic Acid; C105686:SU 5402; D029961:Zebrafish Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D003513:Cycloheximide; D020928:Mitogen-Activated Protein Kinases