title: Zebrafish mutations in Gli-mediated hedgehog signaling lead to lens transdifferentiation from the adenohypophysis anlage.
abstract: It is known that the earliest lens marker delta-crystallin is expressed abundantly in Rathke's pouch of the chicken, suggesting a close relationship between the cell states of the adenohypophysis (pituitary) anlage and the early lens. We show here that the zebrafish midline mutants you-too (yot) and iguana (igu) develop lenses from the adenohypophysis anlage. The early adenohypophysis anlage of normal zebrafish expresses lim3 and six3 but in yot(ty119) mutants the anterior part of the anlage lacks lim3 expression, and instead produces a crystallin-expressing cell population which develops into a large lens structure expressing beta and gamma-crystallins, but is not associated with retina tissues. Among the zebrafish mutants with midline defects, midline lenses were observed in two mutant alleles of yot and an allele of igu, but not in other mutants (syu, con, smh, dtr, uml, spi and lok). Two yot mutant alleles with midline lenses likely encode dominant negative forms of the Gli2 protein which will interfere with transcriptional activation by other Gli proteins. The observation argues that overall inhibition of Shh-Gli signaling leads the adenohypophysis anlage to transdifferentiate into lens.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Osaka, Japan. j61056@center.osaka-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kondoh
authors.forename: M
authors.initials: M
authors.lastname: Uchikawa
authors.forename: H
authors.initials: H
authors.lastname: Yoda
authors.forename: H
authors.initials: H
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Furutani-Seiki
authors.forename: R O
authors.initials: RO
authors.lastname: Karlstrom
mesh_terms: D000483:Alleles; D000818:Animals; D002642:Chick Embryo; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000196:embryology* / Q000378:metabolism; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010903:Pituitary Gland, Anterior / Q000196:embryology* / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D015398:Signal Transduction; D013045:Species Specificity; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: D003459:Crystallins; D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; C118355:gli2a protein, zebrafish