FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain.
The segmentation of the vertebrate hindbrain into rhombomeres is highly conserved, but how early hindbrain patterning is established is not well understood. We show that rhombomere 4 (r4) functions as an early-differentiating signaling center in the zebrafish hindbrain. Time-lapse analyses of zebrafish hindbrain development show that r4 forms first and hindbrain neuronal differentiation occurs first in r4. Two signaling molecules, FGF3 and FGF8, which are both expressed early in r4, are together required for the development of rhombomeres adjacent to r4, particularly r5 and r6. Transplantation of r4 cells can induce expression of r5/r6 markers, as can misexpression of either FGF3 or FGF8. Genetic mosaic analyses also support a role for FGF signaling acting from r4. Taken together, our findings demonstrate a crucial role for FGF-mediated inter-rhombomere signaling in promoting early hindbrain patterning and underscore the significance of organizing centers in patterning the vertebrate neural plate.
Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403-1254, USA. maves@uoneuro.uoregon.edu
Lisa
L
Maves
William
W
Jackman
Charles B
CB
Kimmel
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D016380:Brain Tissue Transplantation; D004268:DNA-Binding Proteins / Q000235:genetics; D051767:Early Growth Response Protein 2; D051518:Fibroblast Growth Factor 3; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051258:MafB Transcription Factor; D008959:Models, Neurological; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012249:Rhombencephalon / Q000196:embryology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D051518:Fibroblast Growth Factor 3; D051258:MafB Transcription Factor; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; C111092:mafb protein, zebrafish; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors