Biomedical subjects

U Gaul

Publications and source records attributed to U Gaul.

24 records · Page 2Linked to original sources

PubMed1989

Single amino acid exchanges in the finger domain impair the function of the Drosophila gene Krüppel (Kr).

Mutations in the Drosophila gene Krüppel (Kr) cause deletions of segments in the embryo and also affect Malpighian tubule development. In the hypomorphic Kr alleles that were analyzed, the defects in the segment pattern and the Malpighian tubules are parallel in strength. We have sequenced the DNA of four Kr alleles that show normal spatial and temporal patterns of Kr-encoded protein expression. Three of the four alleles have single base pair mutations that result in a single amino acid change. The exchanges occur in the putative DNA-binding domain of the Kr protein, which is characterized by four repeats of the zinc finger motif. Sequence comparison of the finger motifs helped to define the structural requirements for the folding of the finger domain to some extent. Our data on the Kr mutants support the view that has emerged from the evolutionary analysis.

Alleles↗

PubMed1989

Analysis of maternal effect mutant combinations elucidates regulation and function of the overlap of hunchback and Krüppel gene expression in the Drosophila blastoderm embryo.

The metameric organisation of the Drosophila embryo is generated early during development, due to the action of maternal effect and zygotic segmentation and homeotic genes. The gap genes participate in the complex process of pattern formation by providing a link between the maternal and the zygotic gene activities. Under the influence of maternal gene products they become expressed in distinct domains along the anteroposterior axis of the embryo; negative interactions between neighboring gap genes are thought to be involved in establishing the expression domains. The gap gene activities in turn are required for the correct patterning of the pair-rule genes; little is known, however, about the underlying mechanisms. We have monitored the distribution of gap and pair-rule genes in wild-type embryos and in embryos in which the anteroposterior body pattern is greatly simplified due to combinations of maternal effect mutations (staufen exuperantia, vasa exuperantia, vasa exuperantia, bicoid oskar, bicoid oskar torsolike, vasa torso exuperantia). We show that the domains of protein distribution of the gap genes hunchback and Krüppel overlap in wild-type embryos. Based on the analysis of the maternal mutant combinations, we suggest an explanation of how this overlap is generated. Furthermore, our data show that different constellations of gap gene activities provide different input for the pair-rule genes, and thus strongly suggest that the overlap of hunchback and Krüppel in wild-type is functional in the formation of the patterns of pair-rule genes.

Animals↗

PubMed1988

Disruption of a putative Cys-zinc interaction eliminates the biological activity of the Krüppel finger protein.

The best-characterized DNA-binding protein structure is the evolutionarily-conserved helix-turn-helix motif. Recently a second motif for DNA-binding proteins, the 'zinc finger', emerged from sequence analysis of TFIIIA, a factor involved in the control of transcription of the Xenopus 5S RNA gene. The finger structure is based on pairs of Cys and His residues which are arranged around a tetrahedrally-coordinated zinc ion. This centre allows the folding of tandemly repeated 'finger loops' which are thought to specify the contact with target DNA. Zinc fingers have been observed in the DNA-binding protein domains of transcriptional activators in yeast and man (R. Tijan, personal communication) and in several regulatory proteins of Drosophila including proteins encoded by members of the gap class of segmentation genes. One of these, Krüppel (Kr), acts at the first level of the segmentation gene hierarchy, and its protein product may bind to DNA. In addition, Kr is required for the development of the malpighian tubules, a posterior internal tissue that forms during later stages of embryogenesis. Here we show that a mutation which results in a conservative amino-acid exchange eliminates Kr+ function. The change occurs in a key position within the putative core structure of a finger, and supports the role of Cys in metal binding as proposed by Klug and coworkers.

Amino Acid Sequence↗

PubMed1987

Pole region-dependent repression of the Drosophila gap gene Krüppel by maternal gene products.

We examined the protein domain of the gap gene Krüppel (Kr) in mutants that affect the establishment of different regions of the segment pattern along the longitudinal axis of the Drosophila embryo. Our data suggest that Kr provides cues for establishing the "central" pattern elements at the blastoderm stage, and that Kr activity is controlled by maternal effect genes acting at the poles. The formation of the Kr protein domain may involve ubiquitous activation of Kr gene expression which, however, is limited by region-specific repression through the action of the maternal anterior and posterior pattern organizer genes. In addition, the formation of the Kr protein domain depends on the activity of gap genes acting adjacent to the Kr domain, but it is independent of subordinate pair-rule gene activities.

Animals↗

PubMed1987

Analysis of Krüppel protein distribution during early Drosophila development reveals posttranscriptional regulation.

We have examined the spatial and temporal patterns of expression of the Krüppel (Kr) protein, a gap gene product, during Drosophila embryogenesis. Antibodies directed against the Kr protein revealed patterns of nuclear staining that represent subpatterns of Kr transcript accumulation in particular tissues. This indicates that the distribution of Kr protein is not a direct response to Kr mRNA accumulation, and that Kr protein expression requires a second level of control in addition to spatially regulated transcription. Our data provide evidence for posttranscriptional control that may involve an intron present in the 5' region of one of the two Kr transcripts. The intron-containing transcript is the only potential source of new Kr protein synthesis after gastrulation. The finding of late and transient patterns of Kr activity in several tissues, such as the developing nervous system, amnion serosa, and muscle precursor cells suggests that Kr activity may be required in several developmental processes after segmentation has been completed.

Animals↗

PubMed1986

A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Krüppel, a Drosophila segmentation gene.

Krüppel (Kr), a segmentation gene of Drosophila, encodes a protein sharing structural features of the DNA-binding "finger motif" of TFIIIA, a Xenopus transcription factor. Low-stringency hybridization of the Kr finger coding sequence revealed multiple copies of homologous DNA sequences in the genomes of Drosophila and other eukaryotes. Molecular analysis of one Kr-homologous DNA clone identified a developmentally regulated gene. Its product, a finger protein, relates to Kr by the invariant positioning of crucial amino acid residues within the finger repeats and by a stretch of seven amino acids connecting the finger loops, the "H/C link." This H/C link is conserved in several nuclear and chromosome-associated proteins of Drosophila and other eukaryotic organisms including mammals. Our results demonstrate a new subfamily of evolutionarily conserved nuclear and possibly DNA-binding proteins that again relate to a Drosophila segmentation gene as in the case of the homeo domain.

Animals↗