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The differentiation of myoblasts to form functional muscle fibers is a consequence of interactions between the mesoderm and ectoderm. The authors examine the role of segment identity in directing these interactions by studying the role of Hox genes in patterning adult muscles in Drosophila. Using the 'four-winged fly' to remove Ultrabithorax function in the developing adult, the authors alter the identity of the ectoderm of the third thoracic segment towards the second and show that this is sufficient to inductively alter most properties of the mesoderm-myoblast number, molecular diversity, and migration pattern-to that of the second thoracic segment. Not all aspects of myogenesis are determined by the segment identity of the ectoderm. The autonomous identity of the mesoderm is important for choosing muscle founder cells in the correct segmental pattern. The authors show this by removal of the function of Antennapedia, the Hox gene expressed in the mesoderm of the third thoracic segment. This results in the transformation of founder cells to a second-thoracic pattern. The authors also report a role for the nervous system in later aspects of muscle morphogenesis by specifically altering Ultrabithorax gene expression in motor neurons. Thus, ectoderm and mesoderm segment identities collaborate to direct muscle differentiation by affecting distinct aspects of the process.

Drosophila melanogaster is one of the most valuable organisms in biological research, particularly in the areas of genetics and developmental biology. Drosophila has been used as a model organism in research for almost a century. The organism is easy to breed and has a short life cycle, making it ideal for the study of genetic mutations. The importance to human health and development lies in the homology of Drosophila genes to those in man, e.g., the homeobox gene complex.

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.

This article undertakes a comparative analysis of the policy making/implementing behavior of elected county executives and appointed county administrators. While both sets of actors are engaged considerably in the policy making and implementing processes, the manner in which they undertake these activities varies, suggesting that form of government and method of (s)election do make a difference in how counties are governed.

The sequence of the Drosophila melanogaster genome presented in this issue of Science is the latest milestone in nine decades of research on this organism. Genetic and physical mapping, whole-genome mutational screens, and functional alteration of the genome by gene transfer were pioneered in metazoans with the use of this small fruit fly. Here we look at some of the instances in which work on Drosophila has led to major conceptual or technical breakthroughs in our understanding of animal genomes.

Drosophila, like many other higher organisms, begins development as a tandem array of more or less identical body segments. During later development, these gradually diverge in morphology until the extensive differentiation of body segments seen in the adult is achieved. The genetic control of this divergence is, by now, moderately well understood. The differentiation of the third thoracic and of all abdominal segments appears to be under the control of a cluster of genes known as the bithorax complex (BX-C) [Lewis, 1978]. As reviewed below, the genes of this complex appear to be differentially regulated along the body axis so that each body segment is characterized by a unique subset of active BX-C genes. The activities of these genes are thought to directly determine segmental identity. Recently, it has been proposed that more anteriorly located segments, including those in the head as well as the first and second thoracic segments, are under the control of another gene cluster that has been named the Antennapedia complex (ANT-C) by Kaufman et al [1980]. These authors suggest that the ANT-C genes may function in a manner analogous to that of the BX-C genes.

Ionizing radiation has long been a promising agent for studying the mechanism of cancer induction. The dose of radiation delivered to a given tissue can usually be determined with much greater precision than can the dose of a chemical agent. By varying the radiation dose, or dose rate, while holding other factors constant, and then measuring the yield of malignant conditions, the investigator can hope to quantitate the kinetics of the cancer induction process. To be sure, there are many obstacles. For example, to assay for malignancy after exposure of somatic cells to radiation is much more difficult than to assay for chromosomal or gene damage after exposure of germ cells to radiation. Doses as low as several hundred rads, when delivered to the organism acutely, may not only kill large numbers of somatic cells but may disrupt the immunological and hormonal systems in such a way as to modify the yield of malignancies in a complex manner.

The phenomenon of pseudoallelism promises to contribute much to our understanding of the gene—how it functions, how it mutates, how it evolves. The functional aspect will be the central theme of this paper. Attention will be focused chiefly on examples of “position pseudoallelism;” namely, those cases in which there is a position effect or phenotypic difference between the “cis-type” (ab/++) and “trans-type” (a+/+b) of double mutant heterozygote. In most of these examples a close functional relationship between the adjoining loci is indicated.

A new method of detecting chromosomal rearrangements in Drosophila melanogaster has been applied to the problem of measuring the biological effects of ionizing radiations from nuclear detonations. The method, itself, is an outgrowth of studies of the bithorax pseudoallelic genes near the middle of the right arm of the third chromosome (Lewis, 1951). It will be called the “bithorax” method. Results of applying it to the detection of X-ray induced rearrangements will be considered first.

STURTEVANT'S multiple allelism hypothesis (Sturtevant 1913) led to the assumption by geneticists during much of the first half of the twentieth century that genes were units indivisible by recombination (reviewed in Lipshitz 2004, pp. 13–18). Disproof of this hypothesis required the discovery of the cis-trans position effect in Drosophila and the recovery of both wild-type and double-mutant recombinants from flies heterozygous for the Star and asteroid rough-eye mutations (Lewis 1942, 1945). A decade later, fine-structure mapping of the rII locus in phage provided definitive proof of intragenic recombination (Benzer 1955). In fact, Oliver (1940) had reported the occurrence of wild-type flies from females heterozygous for the mutations of the lozenge rough-eye series. He interpreted these as revertants, as the title of his article indicates, but he does discuss the possibility that they were the result of recombination. Green and Green (1949) later obtained double and even triple lozenge mutant combinations, thus establishing recombination as the source of the wild-type flies that Oliver had discovered.

In Drosophila melanogaster it has been established that the action of at least some genes is affected by their position in the chromosomes. Critical evidence for this phenomenon of position effect has been given by Sturtevant (1925), Dubinin and Sidorow (1935), and Panshin (1935). Position effects have been detected only in cases in which the relative position of a gene with respect to its neighbors has been altered by a chromosomal rearrangement. It is conceivable that the effective position of a gene may also be changed as a result of a substitution in an adjacent gene of one allele by another. Such a possibility was put to experimental test by Sturtevant (1928) for the dominant mutants, Delta (Dl) and Hairless (H), three units apart in the third chromosome; however, no difference could be demonstrated between Dl H/++ and Dl+/+H.

In a genetics experiment conducted in November 1937 with Drosophila melanogaster and involving the dominant mutant Star (S, in chromosome 2- at locus 1.3; causing an irregularity in the arrangement of eye facets and facet hairs, the homozygote being lethal), a number of flies appeared with small narrow eyes. When these were mated inter se, all of the F1 had abnormal eyes, but these varied in size from that of S/+ (see Table IV) to a narrow slit of red pigment on which only a few facets were scattered. A clue to the manner of inheritance of the type with narrow eyes was found by mating a narrow-eye male to a wild-type female, with the result shown in Table I: Table I F2 Distribution (P1: wild-type ♀ x narrow-eye ♂) February 14, 1938 Wild-type Star Totals..... 82 58

I would like to discuss (a) how important discoveries over the last 100 years help to quantify the risk of cancer in populations exposed to man-made sources of ionizing radiation, and (b) how periodic episodes of contamination of the environment with radioactive elements have created public health problems.

In producing the definitive maps of the giant salivary gland chromosomes of Drosophila melanogaster, C. B. Bridges (1935) interpreted certain structures as tandem gene duplications that had become established in the species.

In 1894, William Bateson1 coined the word ‘homeosis’ in his monumental work Materials for the Study of Variation, Treated with Especial Regard to Discontinuity in the Origin of Species. He gave a surprisingly broad definition of the term as a type of variation in which ‘something has been changed into the likeness of something else’. Goethe2 had already described the phenomenon some 104 years previously in his treatise The Metamorphosis of Plants, and indeed Masters3 made more extensive studies in plants and termed it ‘metamorphy’. However, as metamorphy had quite different meanings in other branches of biology, Bateson proposed ‘homeosis’ as a more specific and useful term, and this name has certainly stood the test of time.

The extensive infraabdominal ( iab ) region contains a number of cis-regulatory elements, including enhancers, silencers, and insulators responsible for directing the developmental expression of the abdominal-A and Abdominal-B homeotic genes at the Drosophila bithorax complex. It is unclear how these regulatory elements are primed for activity early in embryogenesis, but the 100-kb intergenic region is subject to a complex transcriptional program. Here, we use molecular and genetic methods to examine the functional activity of the RNAs produced from this region and their role in cis regulation. We show that a subset of these transcripts demonstrates a distinct pattern of cellular localization. Furthermore, the transcripts from each iab region are discrete and the transcripts do not spread across the insulator elements that delineate the iab regions. In embryos carrying a Mcp deletion, the intergenic transcription pattern is disrupted in the iab4 region and the fourth abdominal segment is transformed into the fifth. We propose that intergenic transcription is required early in embryogenesis to initiate the activation of the Drosophila bithorax complex and define the domains of activity for the iab cis-regulatory elements. We also discuss a possible mechanism by which this may occur.

The correct spatial expression of two Drosophila bithorax complex (BX-C) genes, abdominal-A ( abdA ) and Abdominal-B ( AbdB ), is dependent on the 100-kb intergenic infraabdominal ( iab ) region. The iab region is known to contain a number of different domains ( iab2 through iab8 ) that harbor cis-regulatory elements responsible for directing expression of abdA and AbdB in the second through eighth abdominal segments. Here, we use in situ hybridization to perform high-resolution mapping of the transcriptional activity in the iab control regions. We show that transcription of the control regions themselves is abundant and precedes activation of the abdA and AbdB genes. As with the homeotic genes of the BX-C, the transcription patterns of the RNAs from the iab control regions demonstrate colinearity with the sequence of the iab regions along the chromosome and the domains in the embryo under the control of the specific iab regions. These observations suggest that the intergenic RNAs may play a role in initiating cis regulation at the BX-C early in development.

SIR—The homeotic genes are strikingly conserved between invertebrates and vertebrates. There is conservation, not only of the homeobox sequences, but also of their collinear order on the chromosome. The genes are found in clusters or ‘complexes’, and are arranged on the chromosome in the order of their function along the anteroposterior body axis (for review, see ref. 1). In the fruitfly Drosophila melanogaster; the homeotic genes are split into two separate clusters, the Antennapedia complex (ANT-C) and the Bithorax complex (BX-C), which direct development of the anterior and posterior segments, respectively. We show that in Drosophila virilis, a closely related species2, the homeotic genes are also in two clusters, but the split occurs within the BX-C. The existence of two independent splits in the Drosophila lineage suggests that these flies lack the molecular constraint responsible for the ordered clusters in other animals.

Genetics is a discipline that has successfully used abstractions to attack many of the most important problems of biology, including the study of evolution and how animals and plants develop. The power of genetics to benefit mankind was first recognized by the award of the Nobel Prize in physiology or medicine in 1933 to T. H. Morgan. In the 23 years that had intervened between the time Morgan introduced Drosophila as a new organism for the study of genetics and the award of the Prize, he and his students, especially, A. H. Sturtevant, C. B. Bridges and H. J. Muller, had vastly extended the laws of Mendel as the result of a host of discoveries, to mention only a few: that the genes (Mendel’s factors) are arranged in a linear order and can be placed on genetic maps, that they mutate in forward and reverse directions, that they can exist in many forms, or alleles, and that their functioning can depend upon their position. Purely on the basis of breeding experiments, these early workers were able to deduce the existence of inversions and duplications, for example, before it became possible to demonstrate them cytologically. The list of their achievements is a long one and one that has been put into historical perspective by Sturtevant in A History of Genetics (1).

Background: In the fruitfly Drosophila melanogaster, segment identity is specified by the homeotic 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, bithorax 3 , 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. Conclusion 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.

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.

We have analysed the influence of the bithorax gene complex (BX-C) on two segment-specific features of the central nervous system ofDrosophila larvae: the "presumptive leg neuromeres" (PLN), which are present only in the thoracic ganglia of the larva and develop into the leg neuromeres of the adult fly during metamorphosis; and the "lateral dots" (LD) which are found in the first abdominal as well as thoracic ganglia. We show in both cases that consecutive BX-C genes can suppress the development of these structures. We also show that each gene is expressed in several consecutive segments, leading to an apparent redundancy of the suppression in posterior segments.

The effectiveness of crime deterrence projects such as increased street lighting in ghetto environments has been questioned. The present study not only examines whether increased street lighting in fact reduces crime, but also investigates the attitudes towards local government of citizens who live within that particular environment. The findings illustrate that it would be advisable for governments to address citizen attitudes before undertaking certain crime prevention projects.

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.

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.

The article addresses a deficiency in previous studies of city managers role behavior: the lack of a comprehensive, multidimensional typology through which such behavior might be categorized and explained. Utilizing factor scores generated from a list of fifteen questions in an I.C.M.A. survey questionnaire, the author uses a hierarchial grouping technique to produce seven profiles of managers role behavior. Personal, environmental, and attitudinal correlates are examined to round out each profile.

The study examines productivity improvement efforts among a sample of United States County Administrators. Administrators' actions were divided into “tough” and “soft” approaches which were then examined in light of external and internal environment, governmental actors, duties of the office, management and policy actions and roles, and personal and demographic characteristics. Strong correlates were found in the areas of external environment, managerial role, and personal characteristics.

The way in which genes control the growth and development of an organism is a central problem in biology, and one which is currently under study in diverse forms from phage to man. I would like to discuss an approach to this problem which makes use of a series of pseudoallelic genes in Drosophila. Such series of closely linked genes with related effects have, in several instances, been profitably exploited in the bacteria to learn more about how genes control biochemical pathways. Striking examples are the linked genes controlling histidine biosynthesis in Salmonella (Demerec and Hartman, 1959; Ames and Hartman, 1962), or lactose utilization in E. coli (Jacob and Monod, 1961a,b). It may be anticipated that pseudoallelic series affecting morphological traits, such as the case to be described below, can also be profitably exploited to learn more about how genes control developmental pathways.

It is the purpose of this paper to consider some of the ways in which “pseudoalleles” (McClintock, 1944), or closely linked genes having similar effects, may provide clues to the mode of origin of new kinds of genes.Our underlying thesis will be that in those instances of pseudoallelism in which there is evidence for close functional similarity among the component genes we may come close to seeing the direct results of a process which produces new genes.

In recent months, considerable enthusiasm has been expressed by a number of political and law-enforcement figures in the United States over the possible benefits of heroin maintenance in the treatment of the addict population and the potential benefits in reduction of crime and ultimate rehabilitation. Reference is frequently made to the so-called British system in which heroin is legitimately administered to addicts under legally controlled circumstances in the United Kingdom (unpublished data). 1-4 In March 1972, I was sent to London by the Director of the Bureau of Narcotics and Dangerous Drugs, John E. Ingersoll, to examine the British experience with heroin maintenance. This was an attempt to assist us in assuming a realistic posture regarding the applicability of the British technique in the United States. After a week in the United Kingdom and a number of meetings with knowledgeable officials, I returned with some definite impressions and made some

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.

Dysgenic and radiation-induced types of genetic risks are evaluated for the progeny of persons who received childhood tumor therapy. The dysgenic risks may be quite high for certain types of tumors. The genetic defects of greatest concern following paternal irradiation are likely to be those caused by dominant mutations and unbalanced translocations, whereas chromosomal trisomies may be most important following maternal irradiation. Ways of alleviating these risks are discussed.

The bithorax complex in Drosophila melanogaster is a cluster of homeotic genes that specify developmental pathways for many of the body segments of the fly. The DNA of the bithorax complex has been isolated, and a region of 195,000 base pairs that covers the left half of the complex is described here. The lesions associated with many of the bithorax complex mutants have been identified, and most are due to DNA rearrangements. Most of the spontaneous mutants have insertions of a particular mobile element named "gypsy." This element affects the functions of sequences removed from the site of insertion. Mutant lesions for a given phenotypic class are distributed over large DNA distances of up to 73,000 base pairs.

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.

Mendel was ahead of his time, but he was not so far ahead that he could not arrive at the first great generalizations of genetics—his first and second laws. How fortunate that Mendel did not discover linkage, for he might then have failed to deduce the second law. How fortunate, too, that Mendel, by having chosen to work on peas, failed to discover “gene conversion,” not to mention “meiotic drive,” for he might then have failed to deduce even the first law.

Absorbed doses of radiation from fallout, when averaged over yearly periods and over large numbers of individuals, have usually been assumed to be well below the corresponding doses from natural background sources. Although this assumption may be valid for most body organs, it is unlikely to have been valid for the thyroid glands of the average infant and child in the U.S. The purpose of this note is to point out that for the last few years such thyroids probably have received an annual radiation dose (chiefly, from the beta-rays of radioiodine) that is approximately equal to the annual dose which they receive from natural background radiations.