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E B Lewis

Publications and source records attributed to E B Lewis.

At least 19 recordsLinked to original sources
PubMed1995

Complete sequence of the bithorax complex of Drosophila.

The bithorax complex (BX-C) of Drosophila, one of two complexes that act as master regulators of the body plan of the fly, is included within a sequence of 338,234 bp (SEQ89E). This paper presents the strategy used in sequencing SEQ89E and an analysis of its open reading frames. The BX-C sequence (BXCALL) contains 314,895 bp obtained by deletion of putative genes that are located at each end of SEQ89E and appear to be functionally unrelated to the BX-C. Only 1.4% of BXCALL codes for the three homeodomain-containing proteins of the complex. Principal findings include a putative ABD-A protein (ABD-AII) larger than a previously known ABD-A protein and a putative glucose transporter-like gene (1521 bp) located at or near the bithoraxoid (bxd), infra-abdominal-2 (iab-2) boundary on the opposite strand relative to that of the homeobox-containing genes.

Animals↗
PubMed1995

Sequence analysis of the cis-regulatory regions of the bithorax complex of Drosophila.

The bithorax complex (BX-C) of Drosophila, one of two complexes that act as master regulators of the body plan of the fly, has now been entirely sequenced and comprises approximately 315,000 bp, only 1.4% of which codes for protein. Analysis of this sequence reveals significantly overrepresented DNA motifs of unknown, as well as known, functions in the non-protein-coding portion of the sequence. The following types of motifs in that portion are analyzed: (i) concatamers of mono-, di-, and trinucleotides; (ii) tightly clustered hexanucleotides (spaced < or = 5 bases apart); (iii) direct and reverse repeats longer than 20 bp; and (iv) a number of motifs known from biochemical studies to play a role in the regulation of the BX-C. The hexanucleotide AGATAC is remarkably overrepresented and is surmised to play a role in chromosome pairing. The positions of sites of highly overrepresented motifs are plotted for those that occur at more than five sites in the sequence, when < 0.5 case is expected. Expected values are based on a third-order Markov chain, which is the optimal order for representing the BXCALL sequence.

Amino Acid Sequence↗
PubMed1994

Muscle development in the four-winged Drosophila and the role of the Ultrabithorax gene.

BACKGROUND: In the fruitfly Drosophila melanogaster, segment identity is specified by the homoeotic selector genes of the bithorax and Antennapedia complexes. The functions of these genes in the segmental specification of the Drosophila ectoderm have been well studied, but their roles in muscle development have been relatively poorly investigated. Recent experiments have strongly suggested that homeotic selector genes are directly involved in one aspect of mesodermal patterning during Drosophila embryogenesis. But muscle development is a complex process, requiring for its completion the correct positioning of the epidermis, the nervous system and the developing muscles in a segment-specific manner. Many aspects of homeotic selector gene function in this process remain to be understood. RESULTS: In flies that are homozygous for three mutant alleles (anterobithorax, bithorax3, postbithorax) of the Ultrabithorax gene, the third thoracic segment (T3) is transformed towards the second (T2). The adults have two pairs of wings, but the homeotically transformed T3 (HT3) has only rudimentary indirect flight muscles. We used the 'four-winged' fly to study the role of homeotic selector genes in the development of the indirect flight muscles, which we classify into four 'events'. First, the determination of the segment-specific pattern of myoblasts in the larval thorax; second, the specific pattern of migration of myoblasts during metamorphosis; third, the fusion of myoblasts to form adult indirect flight muscles and fourth, the development of the branching pattern of adult motor innervation. Our study shows that the segmental identity of the epidermis determines the segment-specific pattern and number of myoblasts on the larval discs, and the pattern of their migration during metamorphosis. The segmental identity of the mesoderm, however, is crucial for the fusion of myoblasts to form indirect flight muscles, and also influences the branching pattern of innervation of indirect flight muscles. CONCLUSIONS: Segmental information expressed in the ectoderm, and the autonomous function of homeotic selector genes in the mesoderm, are both required for the complete development of indirect flight muscles.

Alleles↗
PubMed1993

Molecular basis of transabdominal--a sexually dimorphic mutant of the bithorax complex of Drosophila.

Transabdominal (Tab) is a dominant gain-of-function mutation that results in islands of sexually dimorphic abdominal cuticle in the dorsal thorax of the adult fly. This phenotype has complete penetrance and constant expressivity, and we show that it results from ectopic expression of ABD-BII, one of two proteins derived from the Abdominal B (Abd-B) domain of the bithorax complex (BX-C) and one that is normally expressed only in terminal portions of the abdomen. In Tab/+ animals ABD-BII is ectopically expressed in the relevant imaginal "wing" disc as three islands of cells whose location on the fate map corresponds to the three islands of transformed cuticle in each half of the adult thorax. Tab is associated with an inseparable inversion bringing sequences in 90E next to sequences in the transcription unit encoding ABD-BII in 89E. That 90E sequences drive ectopic expression of ABD-BII is indicated by our finding that such sequences in a P-element transformant express the reporter gene's product (beta-galactosidase) in the same three islands of wing disc cells. On morphological grounds, the transformed islands in the adult thorax correspond to subsets of muscle attachment cells. Ectopic expression of a homeodomain protein thus creates a unique and invariant pattern of sexual dimorphism.

Animals↗
PubMed1990

The molecular genetics of the bithorax complex of Drosophila: cis-regulation in the Abdominal-B domain.

In Drosophila the Abdominal-B (Abd-B) domain of the bithorax complex (BX-C) spans over 100 kb and is responsible for specifying the identities of adult abdominal segments five (A5) to nine (A9), inclusive, and correspondingly, neuromeres 10-14 of the embryonic central nervous system. The domain consists of a region coding for two proteins, ABD-BI (54 kd) and ABD-BII (36 kd) and cis-regulatory regions extending from infra-abdominal-5 (iab-5) to iab-9, inclusive. We have used a monoclonal anti-ABD-B antibody to infer that mutants in iab-8 eliminate the expression of ABD-BI in neuromeres 10-13, inclusive, and that mutants in iab-9 eliminate expression of ABD-BII in neuromere 14. ABD-B expression is also analyzed in homozygotes for (i) loss-of-function mutants involving the iab-5, iab-6 and iab-7 regions, (ii) gain-of-function mutants Miscadastral pigmentation (Mcp) and Superabdominal (Sab), and (iii) a trans-regulator, Polycomb (Pc). ABD-B expression along the antero-posterior axis is colinear with the chromosomal order of the cis-regulatory regions. The behavior of rearrangement-associated iab-6 and iab-7 mutants suggests that the enhancer-like region, iab-5, and possibly also iab-6, may be shared between the abd-A and Abd-B domains. Such sharing is proposed as a factor that tends to keep gene complexes intact during evolution.

Abdomen↗
PubMed1989

The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain.

In Drosophila the Abdominal-B (Abd-B) domain of the bithorax complex specifies the identities of several posterior abdominal segments, comprises homeo-protein-coding regions and cis-regulatory regions, and extends from infra-abdominal-5 (iab-5) to iab-8, inclusive. Mutations that eliminate the Abd-B domain act as late embryonic lethals and result in transformations of posterior abdominal segments toward more anterior ones. The Abd-B domain gives rise to a minimum of five homeo-box-containing transcripts, 7.8, 4.7, 4.3, 3.7, and 3.3 kb in length. We examined the structure of the Abd-B domain by sequencing two Abd-B cDNA clones derived from the 4.3- and the 4.7-kb transcripts and the corresponding genomic DNA. The domain spans approximately 100 kb and contains at least eight exons. The 4.7- and 4.3-kb transcripts contain an open reading frame capable of encoding a 54-kD protein. A portion of the deduced protein-coding sequence common to all of the Abd-B transcripts was cloned into an expression vector. The resultant fusion protein then was used to derive a monoclonal antibody specific to Abd-B. By use of that antibody, we identified two embryonic Abd-B proteins, 54 and 36 kD and determined the sum of their segmental distribution by immunohistochemical analysis of whole-mounted embryos and immunofluorescent analysis of dissected embryonic nervous systems. The proteins are distributed in the fourth to the ninth abdominal segments [parasegments (PS) 10-15] inclusive. Embryos homozygous for Polycomb (Pc) show labeling over almost the entire embryo, whereas embryos deficient for the Abd-B domain show no detectable labeling.

Amino Acid Sequence↗
PubMed1987

Transabdominal, a dominant mutant of the Bithorax Complex, produces a sexually dimorphic segmental transformation in Drosophila.

Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus, the Tab/ + notum has sets of short stripes that are black in males and only bordered with black in females. Also, Tab/ + abdominal tergites, A1-A6, inclusive, have small patches of A7-like tergite cuticle. Tab is inseparable from an 89E/90D inversion, whose DNA breakpoint in 89E is at +188 kb in the infra-abdominal-8 (iab-8) region of the BX-C. When probed with a pupal cDNA from the iab-7 region, labeling above background was not detected in wild-type wing discs but was detected in, and confined to, the notal region of Tab/ + wing discs. The Tab/ + phenotype is assumed to result from cis-overexpression of iab-7 in localized regions of segments T2-A6, inclusive.

Animals↗
PubMed1985

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↗
PubMed1985

Regulation of the genes of the bithorax complex in Drosophila.

The BX-C is a set of master control genes that trans-regulate other genes and thereby control much of the segmentation pattern of the fly. The BX-C genes are themselves regulated in cis and trans. Three rules governing cis-regulation of BX-C are applicable over a region extending from Ubx to at least iab-7, a distance of nearly 300 kb on the DNA map: The colinearity (COL) rule: genes are colinear with respect to map location and order of expression along the body axis, the only exception thus far being pbx+; the cis-inactivation (CIN) rule: a mutant lesion in one gene tends to cis-inactivate the wild-type gene(s) immediately distally; and the cis-overexpression (COE) rule: certain mutant lesions in a given gene cause the next most proximal gene to overexpress one segment more anterior to the one in which the latter gene normally expresses. A model is proposed that attempts to account for these rules by invoking a special cis-regulatory entity (E) that diffuses more efficiently along the chromosome than between chromosomes.

Animals↗
PubMed1982

Control of body segment differentiation in Drosophila by the bithorax gene complex.

The bithorax complex is a gene cluster whose function is to regulate still other genes in such a way that each segment of the body commencing with the second thoracic segment and proceeding posteriorly, develops a unique pattern of structures. Numerous cis-regulatory regions have been identified within the complex and are believed to bind to repressor-like substances elaborated by the wild-type alleles of at least two major trans-regulatory genes, Polycomb and extra sex combs. The more proximal is a gene in the complex (with the exception of postbithorax) the more likely it is to be derepressed; the more posterior is a segment in the organism, the greater is the number of BX-C genes that become derepressed in that segment. A gradient in repressor substance(s) and a gradient in affinity of the cis-regulatory regions for repressor can account in a formal sense for the regulation of the BX-C genes themselves.

Animals↗
PubMed1978

A gene complex controlling segmentation in Drosophila.

The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal development. The state of repression of at least four of these genes is controlled by cis-regulatory elements and a separate locus (Polycomb) seems to code for a repressor of the complex. The wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element.

Abdomen↗
PubMed1977

Setting up in private practice. A guide for the newly appointed consultant.

If you are considering going into private practice under the present contract weigh up the cost, seek advice as to prospective earnings, join a partnership if you can, buy sound sensible equipment (second-hand if possible), insure for super-annuation and sickness benefits right away--it is both cheaper and safer. Agree a sensible NHS programme from the start using the advice of the BMA and the Association of Anaesthetists, and, when you are an established practitioner and a young colleague joins you, try to give him a helping hand and sound advice. The sine qua non of survival is co-operation.

Anesthesiology↗