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Development, Vol 126, Issue 6 1189-1200, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
S Martinez, PH Crossley, I Cobos, JL Rubenstein and GR Martin
Department of Morphological Sciences, Faculty of Medicine, University of Murcia, Murcia, Spain.
Beads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9-12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact with the bead formed an outgrowth that protruded laterally from the neural tube. Tissue within such lateral outgrowths developed proximally into isthmic nuclei and distally into a cerebellum-like structure. These morphogenetic effects were apparently due to FGF8-mediated changes in gene expression in the vicinity of the bead, including a repressive effect on Otx2 and an inductive effect on En1, Fgf8 and Wnt1 expression. The ectopic Fgf8 and Wnt1 expression domains formed nearly complete concentric rings around the FGF8-bead, with the Wnt1 ring outermost. These observations suggest that FGF8 induces the formation of a ring-like ectopic signaling center (organizer) in the lateral wall of the brain, similar to the one that normally encircles the neural tube at the isthmic constriction, which is located at the boundary between the prospective midbrain and hindbrain. This ectopic isthmic organizer apparently sends long-range patterning signals both rostrally and caudally, resulting in the development of the two ectopic midbrains. Interestingly, our data suggest that these inductive signals spread readily in a caudal direction, but are inhibited from spreading rostrally across diencephalic neuromere boundaries. These results provide insights into the mechanism by which FGF8 induces an ectopic organizer and suggest that a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain.
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F Marin and P Charnay Hindbrain patterning: FGFs regulate Krox20 and mafB/kr expression in the otic/preotic region Development, January 11, 2000; 127(22): 4925 - 4935. [Abstract] [PDF]
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C Irving and I Mason Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression Development, January 1, 2000; 127(1): 177 - 186. [Abstract] [PDF]
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M Carl and J Wittbrodt Graded interference with FGF signalling reveals its dorsoventral asymmetry at the mid-hindbrain boundary Development, January 12, 1999; 126(24): 5659 - 5667. [Abstract] [PDF]
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A Liu, K Losos, and A. Joyner FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate Development, January 11, 1999; 126(21): 4827 - 4838. [Abstract] [PDF]
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F Ristoratore, M Carl, K Deschet, L Richard-Parpaillon, D Boujard, J Wittbrodt, D Chourrout, F Bourrat, and J. Joly The midbrain-hindbrain boundary genetic cascade is activated ectopically in the diencephalon in response to the widespread expression of one of its components, the medaka gene Ol-eng2 Development, January 9, 1999; 126(17): 3769 - 3779. [Abstract] [PDF]
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C Irving and I Mason Regeneration of isthmic tissue is the result of a specific and direct interaction between rhombomere 1 and midbrain Development, January 9, 1999; 126(18): 3981 - 3989. [Abstract] [PDF]
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