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The gastropod Lottia peitaihoensis as a model to study the body patterning of trochophore larvae.

The body patterning of trochophore larvae is important for understanding spiralian evolution and the origin of the bilateral body plan. However, considerable variations are observed among spiralian lineages, which have adopted varied strategies to develop trochophore larvae or even omit a trochophore stage. Some spiralians, such as patellogastropod mollusks, are suggested to exhibit ancestral traits by producing equal-cleaving fertilized eggs and possessing "typical" trochophore larvae. In recent years, we developed a potential model system using the patellogastropod Lottia peitaihoensis (= Lottia goshimai). Here, we introduce how the species were selected and establish sources and techniques, including gene knockdown, ectopic gene expression, and genome editing. Investigations on this species reveal essential aspects of trochophore body patterning, including organizer signaling, molecular and cellular processes connecting the various developmental functions of the organizer, the specification and behaviors of the endomesoderm and ectomesoderm, and the characteristic dorsoventral decoupling of Hox expression. These findings enrich the knowledge of trochophore body patterning and have important implications regarding the evolution of spiralians as well as bilateral body plans.

Animals

Morphogen gradients and the control of body pattern in insect embryos.

The basic body plan of insects is set up in response to determinants initially localized at the anterior and posterior poles of the egg. Early in development, these determinants give rise to a series of morphogen gradients which in turn trigger a cascade of molecular signals determining the body pattern. This signalling process is outlined and recent experiments testing the roles of these gradient systems in determining anterior and posterior pattern are described. The results of these experiments suggest that anterior pattern is controlled by a single instructive gradient, whereas posterior pattern depends on the overlap of several gradients, each providing only one or a few distinct responses.

Animals

Dynamics of the control of body pattern in the development of Xenopus laevis. IV. Timing and pattern in the development of twinned bodies after reorientation of eggs in gravity.

The mesendodermal anatomy of twinned larval axes is described in relation to the normal single pattern, when twinning has been caused by experimental tilting of eggs before first cleavage. The formation of two origins for gastrulation movements (dorsal lips) and their relatively rapid spread and coalescence to give a circular blastopore, is a predictor of twin formation in individual embryos after treatment. The anatomy of twins where development has been disturbed from the outset in this way is appreciably different from that induced by the later operation of second dorsal lip implantation. It is also variable in a systematic way. The total sizes of cellular allocations to individual notochords and prechordal head patterns are enhanced above normal if they arise relatively close together in the tissue, but significantly reduced if they arise far apart. These and other features of twinned patterns due to precleavage disturbance are discussed in terms of what they might indicate about the physicochemical nature of the body positional system. The results confirm that by a variety of rather simple, nonsurgical manipulations the relative amounts of territory in the egg devoted to different parts of the body can be greatly influenced.

Animals

Differing strategies for organizing anterior and posterior body pattern in Drosophila embryos.

Opposing anterior and posterior morphogen systems specify the segmented body pattern of Drosophila. The anterior morphogen, bicoid, exerts a direct, instructive influence on head and thoracic pattern by triggering different outcomes according to changes in its concentration along the body. In contrast, the posterior morphogen, nanos, simply defines where abdominal patterning can occur by eliminating an otherwise ubiquitous repressor, hunchback protein, from the posterior half of the embryo. Within this hunchback-free domain the pattern of abdominal segments must be specified by other morphogens, possibly by shorter range gradients of the products of zygotic gap genes Kruppel, knirps and tailless.

Animals

Localized surface activity of torso, a receptor tyrosine kinase, specifies terminal body pattern in Drosophila.

The subdivision of the Drosophila body into distinct terminal and central domains depends on the torso (tor) protein, a putative receptor tyrosine kinase that is active at both ends of the early embryo. We show that the tor protein is uniformly expressed along the surface membrane of early embryos despite its localized activity at both poles. Further, we present evidence that polarized activity of this protein depends on other terminal gene functions, one of which may be a localized extracellular ligand generated during oogenesis. Finally, using the temperature-sensitive gain-of-function mutation torRL3, we show that different levels of active tor protein can specify distinct portions of the terminal pattern. Thus, we argue (1) that for functions as a ubiquitous surface receptor that is activated by a spatially restricted ligand, and (2) that localized activity of the tor kinase may generate one or more gradients of intracellular signals that control body pattern.

Animals

Dynamics of the control of body pattern in the development of Xenopus laevis. I. Timing and pattern in the development of dorsoanterior and posterior blastomere pairs, isolated at the 4-cell stage.

Xenopus embryos have been selected in which the second cleavage is occurring in a frontal plane, i.e. one tending to lie at right angles to the prospective plane of bilateral symmetry for the body pattern. Some of these have been used to deduce a map of the disposition of materials for the normal mesodermal pattern (the normal 'fate map') by injecting blastomeres to found fluorescently marked clones from 4- to 32-cell stages. Other such 4-cell embryos have been separated into two isolates across this second cleavage; in fate-map terms, prospective dorsoanterior and posterior isolates. These have been allowed to develop to control axial larval stages, with examination of the time schedule of their gastrulation movements in relation to cofertilized whole controls. The patterns of mesoderm produced have been examined and interpreted in the light of quantitative knowledge about the normal pattern, and our current understanding of the map. A meaningful fate map exists for the egg material even at this early, essentially acellular stage, and it differs appreciably from what might have been expected in view of that traditionally shown for early gastrula stages. The patterns developed in the isolates show that at least in many eggs, widespread information that positively specifies material as to its body position is available from at most 1 h after the events that give rise to bilateral symmetry upon fertilization. This information usually leads to a mosaic development of the appropriate mesodermal part-pattern in dorsoanterior isolates, and frequently allows development that approximates to this in the reciprocal posterior part. Regulation, i.e. the replacement of removed information to specify a development more complete than the normal contribution in isolates, is not observed. The results suggest a revision of former claims for regulative ability in at least this amphibian embryo. They also imply that systems for ascribing position value (positional information) to early embryonic tissue can be diverse in dynamics, even among embryos whose body plans are obviously homologous as are those of vertebrates.

Animals

The restrictive effect of early exposure to lithium upon body pattern in Xenopus development, studied by quantitative anatomy and immunofluorescence.

We have carried out an anatomical study of Xenopus larval and gastrula stages resulting from treatment of synchronous early blastulae for brief periods with Li+. We confirm the proposal that such treatment causes a particular transformation, and partial elimination, of the normal body pattern. Coordinated restriction of pattern, without appreciable loss of cell number, is seen in all three germ layers. The distortion has been investigated by quantitative study of mesoderms at a standard stage, in relation to the normal fate map for mesoderm, and with the help of immunofluorescence on sections for somitic muscle and for blood. In the extreme syndrome, mesoderm arises from all around the blastula as usual, but is symmetrical and corresponds to that arising near the dorsal/anterior meridian of the normally specified egg or embryo with a large posterior subset of the normal pattern values thus missing. The effect is independent of any inhibition of archenteron formation or mesoderm migration (i.e. the cell mechanics of gastrulation) incurred by the treatment. It is also quite separate from a syndrome caused by more prolonged exposure to Li+ during gastrulation. A small, but distinctive, anterior pattern region is also not expressed and, anomalously in relation to their general nature, these forms differentiate considerable blood tissue. We consider the implications of some details of the pattern restriction for our understanding of interaction in the normal development and propose that the Li+ embryo is likely to be useful as a specific 'differential screen', in relation to the normal, during the search for those gene products that mediate initial regionalization of the body.

Animals

Germline autonomy of maternal-effect mutations altering the embryonic body pattern of Drosophila.

Nine maternal-effect loci Drosophila melanogaster were tested in germline mosaics to determine whether the wildtype gene activity is required in somatic or germline components of the maternal ovary. Mutations in these loci affect the anterior-posterior or dorso-ventral body pattern. In all nine loci (torso, trunk, exuperantia, vasa, valois, staufen, tudor, dorsal, Toll) a mutant genotype in the germ cells is sufficient to produce all aspects of the mutant embryonic phenotype, even when those germ cells are surrounded by wildtype somatic tissues.

Animals

A molecular gradient in early Drosophila embryos and its role in specifying the body pattern.

After fertilization, the protein products of the Drosophila homeobox gene caudal (cad) accumulate in a concentration gradient spanning the anteroposterior axis of the developing embryo. Mutations in the cad gene that reduce or eliminate the gradient cause abnormal zygotic expression of at least one segmentation gene (fushi tarazu) and alter the global body pattern.

Animals

Mind-body patterns of symptom generation.

Effective ways for joining family therapy with other treatment modalities are becoming increasingly important as the efficacy of family therapy gains acceptance in the medical and mental health community. When one interfaces family therapy with medical and psychopharmacological treatments, which find the sources of symptoms within individuals, rather than interpersonal systems, careful attention must be paid to the mind and body relationships that guide interactions between family behavior and the somatic physiology of each family member. We present six mind-body patterns of symptom generation found to be particularly useful for designing multimodality treatments and for communicating the treatment rationale to medical and psychiatric clinicians or to family members. Case examples illustrate their clinical use.

Combined Modality Therapy

Dynamics of the control of body pattern in the development of Xenopus laevis. II. Timing and pattern in the development of single blastomeres (presumptive lateral halves) isolated at the 2-cell stage.

Xenopus embryos have been selected in which the first cleavage plane is tending strongly to correspond with that of bilateral symmetry for the future larval pattern. The two blastomeres produced by this cleavage have been separated and allowed to develop as reciprocal pairs of presumptive lateral-half isolates. The early development and the time course of the gastrulation movements, and the qualitative and quantitative aspects of larval mesodermal patterns, have been studied in relation to synchronously fertilized controls. The result is restoration of bilateral symmetry for developmental potential, and production of a pair of small gastrulae and larvae with qualitatively complete body plans but 50% of control cell numbers each (see Kageura & Yamana, 1983). Most commonly, however, the resulting small patterns deviate from the normal range in their proportions in at least one of two ways. The notochord territory is rarely, if ever, under-represented (i.e. notochords contain at least 50% control cell numbers) but it is frequently over-represented, in some cases approximating that of control whole embryos. Reciprocal pairs of isolates thus tend, on average, to produce more notochordal tissue than they would have if developing normally. Secondly, the balance of cell population sizes assigned to somites up and down the axis is altered so that relatively anterior members of the series are less scaled down than those in trunk and tail regions. The mesodermal plan developed by a lateral-half isolate is thus characteristically intermediate between that of a small, harmonious larva (the proportional presumptive fates of the materials, apart from loss of bilaterality), and that of the mosaically developing presumptive dorsoanterior cell pair from the 4-cell stage, discussed in the previous paper. A minority of the lateral isolates does develop a harmonious and thus well-regulated body plan, however, and the normality or otherwise of the schedules of gastrulation timing in isolates seems a good predictor of their morphogenetic performance in this respect. The results are discussed as informing us about the dynamics of the interactions, prior to gastrular stages, that underlie the normal mesoderm development.

Animals

RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos.

In Drosophila embryos, graded activity of the posterior determinant nanos (nos) generates abdominal segmentation by blocking protein expression from maternal transcripts of the hunchback (hb) gene. When active inappropriately at the anterior pole, nos can also block expression of the anterior determinant bicoid (bcd). We show that both regulatory interactions are mediated by similar sequences in the 3' untranslated region of each transcript. These nos response elements (NREs) are both necessary and sufficient to confer nos-dependent regulation, the degree of regulation determined by the number and quality of the elements and the level of nos in vivo. Based on these and other results, we argue that nos acts as a morphogen, controlling hb expression (and hence abdominal pattern) as a function of its concentration-dependent interaction with the NREs.

Animals

Control of Drosophila body pattern by the hunchback morphogen gradient.

Most of the thoracic and abdominal segments of Drosophila are specified early in embryogenesis by the overlapping activities of the hunchback (hb), Krüppel, knirps, and giant gap genes. The orderly expression of these genes depends on two maternal determinants: bicoid, which activates hb transcription anteriorly, and nanos, which blocks translation of hb transcripts posteriorly. Here we provide evidence that the resulting gradient of hb protein dictates where the Krüppel, knirps, and giant genes are expressed by providing a series of concentration thresholds that regulate each gene independently. Thus, hb protein functions as a classical morphogen, triggering several distinct responses as a function of its graded distribution.

Animals

Dynamics of the control of body pattern in the development of Xenopus laevis. III. Timing and pattern after u.v. irradiation of the egg and after excision of presumptive head endo-mesoderm.

A series of Xenopus egg batches has been exposed to doses of u.v. (2537A) light on the vegetal hemisphere at precleavage stages, calculated to result in a range of minimal axial deficiency syndromes in the developing larvae. At the time of onset of gastrulation in synchronously fertilized but non-irradiated batch members, each experimental group was regularly scanned so that small subsamples of embryos could be set aside as showing particular, progressive degrees of delay in onset of the visible gastrulation movements. Such sampling was found to have preselected embryos showing generally progressive degrees of pattern impairment at larval stages, and this observation was extended by histological examination of the anterior axial anatomy. Such examination was also made of the least abnormal-looking members of a series of larvae resulting from excision of the presumptive head endo-mesoderm, traditionally called 'the organizer', from stage-10 gastrulae (Cooke, 1975). The results support the notion that production of the most anterior endo-mesodermal pattern parts (and of their inductive capacities in giving rise to the brain pattern) occurs only in material whose timing, in the onset of gastrulation activity, is close to the normal onset time after fertilization. Either an early failure of the egg to generate a location with the 'position value' corresponding with this extreme of the pattern, or the much later excision of the region from a physiologically normal gastrula, results in a system of pattern formation permanently truncated at its apical (head and dorsal) end. There is no evidence for any dynamic, in the system ascribing position value, that will cause regulative restoration of this cellular state (the most extreme 'activation' for development) in response to its absence after precleavage stages. An earlier statement (Cooke, 1975) that this could occur was based upon inadequate analysis of larvae with an often misleading external anatomy. The present results are discussed as supporting the overall view of the early Xenopus patterning system that has been developed in the previous two papers of the series.

Animals

Establishment and refinement of segmental pattern in the Drosophila embryo: spatial control of engrailed expression by pair-rule genes.

We are examining the development of the segmental body pattern of Drosophila by immunolocalization of engrailed, a developmental regulatory protein that maintains segmental subdivisions in the embryo, and is expressed in a spatially restricted (striped) manner that persists while the body pattern is being established and refined. A regulatory network among pair-rule segmentation genes establishes the striped pattern of engrailed expression. In general, mutations in particular pair-rule genes affect either even- or odd-numbered engrailed stripes. For example, fushi tarazu or odd-paired mutations delete even-numbered stripes, whereas paired mutations delete odd-numbered stripes. An analysis of engrailed expression in other mutants, including even-skipped odd-skipped double mutants, indicates that some pair-rule genes play a rule in establishing the correct width and position of engrailed stripes. Overall, the changes in engrailed pattern have consequences for final embryonic body pattern. Thus, the pair-rule loci, acting through engrailed, establish an early, general outline of body pattern. However, in several pair-rule mutants, engrailed patterns are dynamic, suggesting that as later events build upon this general rule to form the final body pattern, adjustments are made in response to the earlier pair-rule defect--that is, the pattern regulates.

Animals

Skinfold and body circumferences as measures of body fat patterning in a French female active population: relationships with the metabolic risk profile.

Body mass index (BMI), various anthropometric indices of abdominal fat distribution and some metabolic variables (blood lipids, fasting glucose, blood pressure) were measured in 408 French-born women from an occupational population who volunteered for the study. The aim of the study was to determine the best index for describing the relationships between the body fat pattern and the metabolic risk profile. The four age-adjusted circumference ratios (waist/hip, waist/thigh, xiphoid/hip, xiphoid/thigh) showed similar associations with the metabolic variables whereas the three age-adjusted skinfold ratios (epigastric/thigh, mesogastric/thigh, hypogastric/thigh) tended to be more weakly associated with the metabolic variables, particularly with apolipoprotein (Apo) B and fasting glucose. Multiple regression analyses showed that age-adjusted BMI was significantly related to high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A and Apo B, and blood pressure, independently of abdominal fat distribution. After controlling for the effects of BMI, the waist/thigh ratio remained significantly associated to triglyceride, Apo B, fasting glucose, and systolic blood pressure, whereas the waist/hip ratio and the mesogastric/thigh skinfold ratio were significantly related only to triglyceride and systolic blood pressure independently of BMI. With the exception of triglyceride and fasting glucose, the degree of association between the metabolic variables and the abdominal fat distribution tended to be weaker than that observed with the BMI. These results emphasize the importance of the global corpulence in the levels of metabolic variables. However, all indices of abdominal fat distribution were, to varying degrees, independently associated with an unfavorable metabolic profile. Among them, the waist/thigh circumference ratio seems to be a useful indicator of the body fat pattern in women.

Adipose Tissue