Reference - Detail
|Author||Roy NM, Sagerström CG.|
|Title||An early Fgf signal required for gene expression in the zebrafish hindbrain primordium.|
|Journal||Brain Res. Dev. Brain Res.|
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.
|MeSH||Animals Body Patterning / drug effects Body Patterning / physiology Cells, Cultured Cycloheximide / pharmacology DNA-Binding Proteins Embryo, Nonmammalian Fibroblast Growth Factors / chemistry Fibroblast Growth Factors / physiology* Gastrula / drug effects Gastrula / metabolism Gene Expression Regulation, Developmental / drug effects Gene Expression Regulation, Developmental / physiology* Immunohistochemistry / methods In Situ Hybridization / methods Mesoderm / drug effects Mesoderm / metabolism Microinjections / methods Mitogen-Activated Protein Kinases / metabolism Neurons / drug effects Neurons / physiology Oligonucleotides, Antisense / pharmacology Organizers, Embryonic / drug effects Organizers, Embryonic / physiology Protein Synthesis Inhibitors / pharmacology Pyrroles / pharmacology RNA, Messenger / biosynthesis Receptors, Fibroblast Growth Factor / antagonists & inhibitors Receptors, Fibroblast Growth Factor / genetics Receptors, Fibroblast Growth Factor / metabolism Receptors, Retinoic Acid / metabolism Reverse Transcriptase Polymerase Chain Reaction / methods Rhombencephalon / drug effects Rhombencephalon / embryology Rhombencephalon / metabolism* Signal Transduction / drug effects Signal Transduction / physiology* Spinal Cord / cytology Spinal Cord / metabolism Time Factors Tretinoin / pharmacology Zebrafish Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*|