Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning.
Zebrafish you-too (yot) mutations interfere with Hedgehog (Hh) signaling during embryogenesis. Using a comparative synteny approach, we isolated yot as a zinc finger transcription factor homologous to the Hh target gli2. Two alleles of yot contain nonsense mutations resulting in carboxy-terminally truncated proteins. In addition to causing defects in midline development, muscle differentiation, and retinal axon guidance, yot mutations disrupt anterior pituitary and ventral forebrain differentiation. yot mutations also cause ectopic lens formation in the ventral diencephalon. These findings reveal that truncated zebrafish Gli2 proteins interfere with Hh signaling necessary for differentiation and axon guidance in the ventral forebrain.
Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016 USA. karlstrom@bio.umass.edu
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Karlstrom
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Talbot
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Schier
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D047108:Embryonic Development; D008040:Genetic Linkage / Q000235:genetics; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016548:Prosencephalon / Q000196:embryology / Q000254:growth & development; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins; D000075746:Zinc Finger Protein Gli2
D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D011506:Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000075746:Zinc Finger Protein Gli2; C118355:gli2a protein, zebrafish