Biomedical subjects

I A Sulston

Publications and source records attributed to I A Sulston.

4 recordsLinked to original sources

PubMed1998

Altered patterns of gene expression in Tribolium segmentation mutants.

Embryos homozygous for the godzilla, jaws, or kraken mutations of Tribolium castaneum have characteristic defects in segmentation. Here, we examine the expression of Tribolium genes homologous to Drosophila segmentation genes in these mutants to define similarities and differences in the process of segmentation in the two insects. The godzilla mutation disrupts segmentation and alters the expression of Even-skipped (Eve) throughout the germ band. godzilla, therefore, acts at an early step in the segmentation gene hierarchy; the evidence suggests it could be the Tribolium homologue of the eve gene. The jaws mutation causes deletion of most of the abdomen; this defect appears to be correlated with the failure of Eve to resolve into a striped pattern of expression, jaws also causes homeotic transformations in the thorax and the first abdominal segment; this transformation is accompanied by ectopic expression of the homeotic gene maxillopedia in the transformed segments. The kraken mutant disrupts patterning within each segment and, like Drosophila segment polarity mutants, disrupts the maintenance of the normal expression domain of Engrailed. This analysis suggests that late stages of segmentation are similar in Tribolium and Drosophila, although there are clear differences in early steps of segmentation in the two insects.

Animals↗

PubMed1996

Embryonic patterning mutants of Tribolium castaneum.

The identification and analysis of genes controlling segmentation in Drosophila melanogaster has opened the way for understanding similarities and differences in mechanisms of segmentation among the insects. Homologues of Drosophila segmentation genes have been cloned and their expression patterns have been analyzed in a variety of insects, revealing that the patterns of expression of many genes are conserved. Conserved expression patterns do not, however, necessarily reflect conserved gene function. To address gene function, we have conducted a screen for mutations that alter embryonic patterning of the beetle, Tribolium castaneum. One of the mutations isolated, godzilla, affects early steps in the segmentation process in the whole animal, like Drosophila pair-rule mutants. Another mutation, jaws, is novel: it caused both a dramatic homeotic transformation in the thorax and first abdominal segment as well as a deletion of most of the segments of the abdomen. In Tribolium and other intermediated germ band insects, the anterior segments of the embryo are determined in the syncytium of the blastoderm, whereas the abdominal segments proliferated in the cellular environment. Both the godzilla and jaws mutations affect segments that are formed in the syncytium differently from those that are formed after cellularization. These regionally specific phenotypes may reflect the different patterning mechanisms that must be employed by the anterior and posterior regions of an intermediated germ insect.

Animals↗

PubMed1990

Dominant maternal-effect mutations causing embryonic lethality in Caenorhabditis elegans.

We undertook screens for dominant, temperature-sensitive, maternal-effect embryonic-lethal mutations of Caenorhabditis elegans as a way to identify certain classes of genes with early embryonic functions, in particular those that are members of multigene families and those that are required in two copies for normal development. The screens have identified eight mutations, representing six loci. Mutations at three of the loci result in only maternal effects on embryonic viability. Mutations at the remaining three loci cause additional nonmaternal (zygotic) effects, including recessive lethality or sterility and dominant male mating defects. Mutations at five of the loci cause visible pregastrulation defects. Three mutations appear to be allelic with a recessive mutation of let-354. Gene dosage experiments indicate that one mutation may be a loss-of-function allele at a haploin sufficient locus. The other mutations appear to result in gain-of-function "poison" gene products. Most of these become less deleterious as the relative dosage of the corresponding wild-type allele is increased; we show that relative self-progeny viabilities for the relevant hermaphrodite genotypes are generally M/+/+ greater than M/+ greater than M/M/+ greater than M/Df greater than M/M, where M represents the dominant mutant allele.

Animals↗

PubMed1990

Mutations affecting the meiotic and mitotic divisions of the early Caenorhabditis elegans embryo.

We describe interactions between maternal-effect lethal mutations in four genes of Caenorhabditis elegans whose products appear to be involved in the meiotic and mitotic divisions of the one-cell embryo. Mitosis is disrupted by two dominant temperature-sensitive gain-of-function maternal-effect lethal mutations, mei-1(ct46) and mel-26(ct61), and by recessive loss-of-function maternal-effect lethal mutations of zyg-9. The phenotypic defects resulting from these mutations are similar. Doubly mutant combinations show a strong enhancement of the maternal-effect lethality under semipermissive conditions, suggesting that the mutant gene products interact. We isolated 15 dominant suppressors of the gain-of-function mutation mei-1(ct46). Thirteen of these suppressors are apparently intragenic, but 11 of them suppress in trans as well as cis. Two extragenic suppressors define a new gene, mei-2. The suppressor mutations in these two genes also result in recessive maternal-effect lethality, but with meiotic rather than mitotic defects. Surprisingly, most of these suppressors are also able to suppress mel-26(ct61) in addition to mei-1(ct46). The products of the four genes mei-1, mei-2, zyg-9 and mel-26 could be responsible for some of the specialized features that distinguish the meiotic from the mitotic divisions in the one-cell embryo.

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