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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1997-4-7
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pubmed:abstractText |
The developing vertebrate mesencephalon shows a rostrocaudal gradient in the expression of a number of molecular markers and in the cytoarchitectonic differentiation of the tectum, where cells cease proliferating and differentiate in a rostral to caudal progression. Tissue grafting experiments have implicated cell signalling by the mesencephalic-metencephalic (mid-hindbrain) junction (or isthmus) in orchestrating these events. We have explored the role of Wnt-1 and FGF8 signalling in the regulation of mesencephalic polarity. Wnt-1 is expressed in the caudal mesencephalon and Fgf8 in the most rostral metencephalon. Wnt-1 regulates Fgf8 expression in the adjacent metencephalon, most likely via a secondary mesencephalic signal. Ectopic expression of Fgf8 in the mesencephalon is sufficient to activate expression of Engrailed-2 (En-2) and ELF-1, two genes normally expressed in a decreasing caudal to rostral gradient in the posterior mesencephalon. Ectopic expression of Engrailed-1 (En-1), a functionally equivalent homologue of En-2 is sufficient to activate ELF-1 expression by itself. These results indicate the existence of a molecular hierarchy in which FGF8 signalling establishes the graded expression of En-2 within the tectum. This in turn may act to specify other aspects of A-P polarity such as graded ELF-1 expression. Our studies also reveal that FGF8 is a potent mitogen within the mesencephalon: when ectopically expressed, neural precursors continue to proliferate and neurogenesis is prevented. Taken together our results suggest that FGF8 signalling from the isthmus has a key role in coordinately regulating growth and polarity in the developing mesencephalon.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ELF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Elf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/En1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fgf8 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 8,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/engrailed 2 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0950-1991
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
124
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
959-69
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9056772-Animals,
pubmed-meshheading:9056772-Body Patterning,
pubmed-meshheading:9056772-Brain,
pubmed-meshheading:9056772-DNA-Binding Proteins,
pubmed-meshheading:9056772-Diencephalon,
pubmed-meshheading:9056772-Fibroblast Growth Factor 8,
pubmed-meshheading:9056772-Fibroblast Growth Factors,
pubmed-meshheading:9056772-Growth Substances,
pubmed-meshheading:9056772-Homeodomain Proteins,
pubmed-meshheading:9056772-Mesencephalon,
pubmed-meshheading:9056772-Mice,
pubmed-meshheading:9056772-Mice, Transgenic,
pubmed-meshheading:9056772-Mutagenesis,
pubmed-meshheading:9056772-Nerve Tissue Proteins,
pubmed-meshheading:9056772-Nuclear Proteins,
pubmed-meshheading:9056772-Phenotype,
pubmed-meshheading:9056772-Pons,
pubmed-meshheading:9056772-Proto-Oncogene Proteins,
pubmed-meshheading:9056772-Signal Transduction,
pubmed-meshheading:9056772-Transcription Factors,
pubmed-meshheading:9056772-Wnt Proteins,
pubmed-meshheading:9056772-Wnt1 Protein,
pubmed-meshheading:9056772-Zebrafish Proteins
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pubmed:year |
1997
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pubmed:articleTitle |
Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain.
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pubmed:affiliation |
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, Cambridge, MA 02138, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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