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M Peifer

Publications and source records attributed to M Peifer.

63 records · Page 4Linked to original sources

Regulatory elements of the bithorax complex that control expression along the anterior-posterior axis.

The Drosophila bithorax complex (BX-C) controls segmental development by selectively deploying three protein products, Ubx, abd-A and Abd-B, within specific segments along the body axis. Expression of these products within any one segment (or, more accurately, parasegment) is affected by mutations clustered in a particular region of the BX-C. The regulatory regions defined by this genetic analysis span 20-50 kb and there is one region for each segmental unit. Here we describe regulatory elements from several of these regions, identified by fusion to a Ubx-lacZ gene and analysis in germline transformants. A small DNA fragment from the abx region programs expression with an anterior boundary in the second thoracic segment (parasegment 5). This anterior limit is appropriate, since the abx region normally controls Ubx in parasegment 5. Other regulatory regions of the BX-C that control development of parasegments 6, 7 or 8 contain similar regulatory elements that program expression with anterior limits in parasegments 6, 7 or 8, respectively. These experiments define a class of BX-C regulatory elements that control expression along the anterior-posterior axis. The early appearance of the lacZ patterns in embryos suggests a role for these elements in the initial activation of expression from the BX-C.

Animals↗

Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity.

We characterized a gene, extradenticle, which seems to interact with a specific subset of Drosophila homeo domain proteins, possibly affecting their target specificity. This interpretation is based on an examination of the zygotic and maternal effect phenotypes of extradenticle mutations. In embryos with reduced levels of extradenticle gene product, anterior and posterior segmental transformations occur. Segmental identity in Drosophila is mediated by the products of the Antennapedia and bithorax complexes. These homeo domain proteins are thought to regulate different target genes specifically in each segment, resulting in different morphologies. extradenticle alters segmental identity without affecting the pattern of expression of homeotic genes. Genetic tests demonstrate that in extradenticle mutants, the homeotic proteins are functional and act in their normal segmental domains, yet segmental identities are altered. Even when homeotic proteins are ectopically expressed under the control of a heterologous promoter, extradenticle mutations affect their consequences. Thus, in the absence of sufficient extradenticle product, altered segmental morphology results from alteration of the functional consequences of specific homeo domain proteins, possibly through alterations in their target gene specificity. extradenticle is also expressed maternally. Complete removal of extradenticle, maternally and zygotically, leads to specific alterations in segmentation, many of which result from failure to maintain the expression of the homeo domain protein engrailed.

Animals↗

Construction of large DNA segments in Escherichia coli.

Recombinant DNA clones containing large pieces of DNA are useful in the study of large genetic units, but these are difficult to make in most bacterial cloning vectors. A strategy is described that uses general and site-specific recombination to construct large pieces of eukaryotic DNA from smaller cloned segments. The large clones are propagated on F factor-based plasmids in Escherichia coli. They can be easily modified to introduce mutations or rearrangements. These techniques were applied to the construction of large DNA segments from the bithorax complex of Drosophila.

DNA, Recombinant↗

Sequences of the gypsy transposon of Drosophila necessary for its effects on adjacent genes.

The Drosophila melanogaster transposon gypsy is the cause of numerous spontaneous mutations, most of which are suppressible by mutations in the suppressor of Hairy wing [su(Hw)] locus. We have examined the phenotype of four revertants of the gypsy element-induced mutation bithoraxoid1 (bxd1) and determined the molecular basis of these reversions. All four revertants have undergone deletions within the gypsy element. The altered gypsy element from one of the partial revertants has been cloned. It has a deletion of only 109 base pairs near the 5' end of the gypsy transcription unit. Similar deletion gypsy elements exist elsewhere in the Drosophila genome. We discuss a mechanism by which the 109-base segment might affect the bxd phenotype.

Animals↗

The anterobithorax and bithorax mutations of the bithorax complex.

The anterobithorax (abx) and bithorax (bx) genes together direct the development of the posterior second and anterior third thoracic segments of the fruit fly. We have characterized the phenotypes and DNA lesions of 19 abx and bx alleles. abx and bx mutations differ both in the nature and location of their DNA lesions, forming two clusters within a relatively small region of the Ultrabithorax transcription unit. Correlation between phenotype and DNA lesion suggests the presence of two or more genetic elements in this region distinct from the Ultrabithorax transcript. Mutant transformations do not strictly obey segmental or parasegmental boundaries. Most of the bx mutations result from insertions of the mobile element gypsy. The strength of these alleles varies in a regular way dependent on the position and orientation of the gypsy element. We propose models for gypsy element action and bithorax complex expression in the light of these results.

Animals↗

The abdominal region of the bithorax complex.

The homeotic mutations in the right half of the bithorax complex of Drosophila cause segmental transformations in the second through the eighth segments of the fly. A chromosomal walk in the bithorax complex has now been extended 215 kb through the right half of the complex, and lesions for over 40 mutations have been located on the DNA map. The mutations can be grouped in a series of phenotypic classes, one for each abdominal segment, although each mutation typically affects more than one segment. The mutant lesions of each class are clustered, and they are aligned on the chromosome in the order of the body segments that they affect. Complementation tests suggest interactions between widely spaced DNA regions; indeed, the right half cannot be split anywhere without some loss of function.

Abdomen↗