Isolation of a Pax-6 homolog from the ribbonworm Lineus sanguineus.

Loosli, Felix; Kmita-Cunisse, Marie; Gehring, Walter

doi:10.1073/pnas.93.7.2658

Cited by 74 publications

(50 citation statements)

References 25 publications

(16 reference statements)

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“…The L. sanguineus genomic library used is a Fix II library prepared with MboI partially digested DNA (31). Highstringency screening of the library was performed as described by Sambrook et al (32).…”

Section: Methodsmentioning

confidence: 99%

Homeobox genes in the ribbonwormLineus sanguineus: Evolutionary implications

Kmita-Cunisse

Loosli²,

Bièrne

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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From our current understanding of the genetic basis of development and pattern formation in Drosophila and vertebrates it is commonly thought that clusters of Hox genes sculpt the morphology of animals in specific body regions. Based on Hox gene conservation throughout the animal kingdom it is proposed that these genes and their role in pattern formation evolved early during the evolution of metazoans. Knowledge of the history of Hox genes will lead to a better understanding of the role of Hox genes in the evolution of animal body plans. To infer Hox gene evolution, reliable data on lower chordates and invertebrates are crucial. Among the lower triploblasts, the body plan of the ribbonworm Lineus (nemertini) appears to be close to the common ancestral condition of protostomes and deuterostomes. In this paper we present the isolation and identification of Hox genes in Lineus sanguineus. We find that the Lineus genome contains a single cluster of at least six Hox genes: two anterior-class genes, three middle-class genes, and one posterior-class gene. Each of the genes can be definitely assigned to an ortholog group on the basis of its homeobox and its f lanking sequences. The most closely related homeodomain sequences are invariably found among the mouse or Amphioxus orthologs, rather than Drosophila and other invertebrates. This suggests that the ribbonworms have diverged relatively little from the last common ancestors of protostomes and deuterostomes, the urbilateria.

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Section: Methodsmentioning

confidence: 99%

Homeobox genes in the ribbonwormLineus sanguineus: Evolutionary implications

Kmita-Cunisse

Loosli²,

Bièrne

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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“…1 The sporadic cases can be part of the WAGR syndrome (Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation) caused by a chromosomal deletion in the 11p13 region. 2 The human PAX6 gene was cloned in 1991 by positional cloning, 3 and has been isolated from both vertebrates and invertebrates including mouse, 4,5 quail, 6 rat, 7 chicken, 8 zebrafish, 9,10 Drosophila melanogaster, 11 sea urchin, 12 Caenorhabditis elegans, 13,14 ribbonworm Lineus sanguineus, 15 ascidian Phallusia mammillata 16 and Xenopus laevis. 17 The human PAX6 gene spans 22 kb and consists of 14 exons.…”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype

Grønskov

Rosenberg²,

Sand

et al. 1999

Eur J Hum Genet

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Mutations in the developmental control gene PAX6 have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. The inheritance is autosomal dominant with high penetrance but variable expressivity. Here we describe a mutational analysis of 27 Danish patients using a dideoxy fingerprinting method, which identified PAX6 mutations in 18 individuals with aniridia. A thorough phenotype description was made for the 18 patients. A total of 19 mutations, of which 16 were novel, are described. Among these were five missense mutations which tended to be associated with a milder aniridia phenotype, and in fact one of them seemed to be non-penetrant. Four of the five missense mutations were located in the paired domain. We also describe a third alternative spliced PAX6 isoform in which two of the four missense mutations would be spliced out. Our observations support the concept of dosage effects of PAX6 mutations as well as presenting evidence for variable expressivity and gonadal mosaicism.

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“…The paired box motif, originally identified in the Drosophila segmentation gene paired (11), is conserved in the genome of diverse organisms ranging from Drosophila to humans (12). The PAX6 genes are conserved in both vertebrates and invertebrates, including humans (3,4), mice (13)(14), quail (15), chicks (16), Xenopus (17), zebrafish (18,19), Drosophila (20), sea urchins (21), squid (22), and ribbonworms Lineus sanguineus (23) and Caenorhabditis elegans (24,25). Mutations in Pax6 are responsible for several naturally occurring mutant phenotypes including aniridia in humans, small-eye in rodents (14,26,27), and eyeless in Drosophila (20).…”

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confidence: 99%

Dissection of the Transactivation Function of the Transcription Factor Encoded by the Eye Developmental Gene PAX6

Tang

Singh

Saunders

1998

Journal of Biological Chemistry

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PAX6 is a transcription activator that regulates eye development in animals ranging from Drosophila to human. The C-terminal region of PAX6 is proline/serine/ threonine-rich (PST) and functions as a potent transactivation domain when attached to a heterologous DNAbinding domain of the yeast transcription factor, GAL4. The PST region comprises 152 amino acids encoded by four exons. The transactivation function of the PST region has not been defined and characterized in detail by in vitro mutagenesis. We dissected the PST domain in two independent systems, a heterologous system using a GAL4 DNA-binding site and the native system of PAX6. Our data consistently showed that in both systems all four constituent exons of the PST domain are responsible for the transactivation function. The four exon fragments act synergistically to stimulate transcription, although none of them can function individually as an independent transactivation domain. Combinations of two or more exon fragments can reconstitute substantial transactivation activity when fused to the DNAbinding domain of GAL4, but they surprisingly do not produce much activity in the context of native PAX6, although the mutant PAX6 proteins are stable and their DNA-binding function remains unaffected. Our data suggest that these mutants may antagonize the wildtype PAX6 activity by competing for target DNA-binding sites. We conclude that the PAX6 protein contains an unusually large transactivation domain that is evolutionarily conserved to a high degree and that its full transactivation activity relies on the synergistic action of the four exon fragments.

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Isolation of a Pax-6 homolog from the ribbonworm Lineus sanguineus.

Cited by 74 publications

References 25 publications

Homeobox genes in the ribbonwormLineus sanguineus: Evolutionary implications

Homeobox genes in the ribbonwormLineus sanguineus: Evolutionary implications

Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype

Dissection of the Transactivation Function of the Transcription Factor Encoded by the Eye Developmental Gene PAX6

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