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At least 91 records · Page 5Linked to original sources

PubMed1992

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals↗

PubMed1992

The Drosophila segmentation gene runt has an extended cis-regulatory region that is required for vital expression at other stages of development.

The Drosophila runt gene functions in several developmental pathways during embryogenesis. This gene was initially characterized due to the pivotal role that it plays in the genetic regulatory network that establishes the segmented body pattern. Recently it was found that this X-chromosome-linked gene is one of several dosage-sensitive, X-linked components that is involved in activating the Sex-lethal gene in blastoderm stage female embryos. Finally, this gene is also extensively re-expressed in later stages of embryogenesis in the developing nervous system where it plays an important role in the development of specific neural lineages. We have initiated an analysis of the runt cis-regulatory region in order to investigate runt's roles in these (and other) developmental pathways. Analysis of both the function and the expression patterns of runt genes with truncated cis-regulatory regions indicates that there are multiple elements that make quantitative contributions to runt regulation during segmentation. We find that sequences that are more than 8.5 kb upstream of the runt promoter are necessary for normal expression during the post-blastoderm stages of embryogenesis. Genetic experiments indicate that the post-blastoderm expression of runt is vital to the organism.

Alleles↗

PubMedDate not supplied

Permanent distortion of positional system of Xenopus embryo by brief early perturbation in gravity.

The formation of a body plan from an initially radially symmetrical egg during animal development is presumed to involve a 'positional system'and a subsequent mechanism of local response to position values provided by this system. Early gene products intimately connected with the latter response mechanism have been identified in Drosophila, and because these share conserved sequences with possible counterparts in vertebrates , there is renewed interest in understanding the physiological nature of the positional system itself in a vertebrate embryo. In the frog Xenopus, body position value appears to be specified in outline across much of the egg material by stages comprising a few cells, after only approximately 2h of development. This is already suggestive of a structural or mechanical recording system rather than a diffusion-controlled gradient. I describe here an experiment aimed at perturbing the positional system by causing gravity-driven rearrangements within eggs which conflict with their own, self-organizing rearrangements near the time of the first cleavage. The system appears to retain its full regulatory properties during only a brief time interval, so that records of positional profiles disturbed at the close of that interval are permanent, and give rise to systematically abnormal body patterns in otherwise healthy larvae. The results are inconsistent with the notion that Xenopus primary pattern results from a set of determinant 'plasms' in the egg, or from a mechanism dominated by long-range diffusion of molecules.

Animals↗

PubMedDate not supplied

Maternal control of Drosophila segmentation gene expression.

Several genes have been identified that are involved in establishing the segmented body pattern during development of the fruit-fly Drosophila melanogaster. These fall into several classes on the basis of the kind of alteration to the wild-type segmentation pattern observed in mutant embryos. For example, mutations of the pair-rule class, such as fushi tarazu (ftz), cause the deletion of pattern elements with a two-segment periodicity; those of the gap class, such as knirps, cause the deletion of contiguous groups of segments. The availability of antibodies against the ftz protein has allowed its spatial pattern of expression to be studied during the development of wild-type and mutant embryos. The aim of the latter kind of experiment is to investigate possible interactions between these important genes. We have recently reported that knirps mutations cause a striking alteration to the pattern of transverse stripes of ftz expression usually seen during embryogenesis. Knirps is a zygotically-expressed gene, but recently a class of maternally-active genes has been identified that causes similar defects in pattern formation. We have now investigated the pattern of ftz expression in mutants of this class and have found that while they do have features seen in knirps mutants, they also exhibit significant differences between the different mutations reflecting the distinct but overlapping domains of gene activity. These observations demonstrate that maternally-active segmentation genes regulate zygotic gene expression, and that some of their effects on ftz may be directed through the knirps gene.

Animals↗

PubMed1988

Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps.

The body pattern along the anterior-posterior axis of the insect embryo is thought to be established by two organizing centres localized at the ends of the egg. Genetic analysis of the polarity-organizing centres in Drosophila has identified three distinct classes of maternal effect genes that organize the anterior, posterior and terminal pattern elements of the embryo. The factors provided by these gene classes specify the patterns of expression of the segmentation genes at defined positions along the longitudinal axis of the embryo. The system responsible for organizing the posterior segment pattern is a group of at least seven maternal genes and the zygotic gap gene knirps (kni). Their mutant phenotype has adjacent segments in the abdominal region of the embryo deleted. Genetic analysis and cytoplasmic transplantation experiments suggested that these maternal genes are required to generate a 'posterior activity' that is thought to activate the expression of kni (reviewed in ref. 2). The molecular nature of the members of the posterior group is still unknown. Here we report the molecular characterization of the kni gene that codes for a member of the steroid/thyroid receptor superfamily of proteins which in vertebrates act as ligand-dependent DNA-binding transcription regulators.

Abdomen↗

PubMed1988

cis-acting sequences responsible for anterior localization of bicoid mRNA in Drosophila embryos.

The anterior body pattern of Drosophila melanogaster is specified in large part by the protein product of the bicoid (bcd) gene which functions as a graded morphogen with its peak of expression at the anterior pole of the embryo. Formation of the gradient is dependent on prior localization of bcd messenger RNA at the anterior pole of the egg cell during oogenesis. Here we demonstrate that a discrete portion of the bcd mRNA is necessary for anterior localization of the bcd transcript and is sufficient to cause localization of heterologous transcripts. The sequences responsible for localization appear to span an interval of about 625 base pairs in the 3' untranslated portion of the bcd mRNA and to include regions capable of forming extensive secondary structure. Transcripts from bcd are synthesized predominantly, if not exclusively, in the nurse cells and then transported to the oocyte by connections at the prospective anterior pole. Our findings support the proposal that bcd transcripts are selectively recognized and trapped as they enter the anterior tip of the oocyte, and suggest that this localization process is mediated by anchored sequence-specific receptors in the oocyte cytoplasm.

Animals↗

PubMed1992

Loss of gene function through rapid mitotic cycles in the Drosophila embryo.

The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development.

Amino Acid Sequence↗

PubMed1987

Physical characteristics of patients with herniated intervertebral lumbar discs.

In an attempt to determine whether certain physical characteristics discriminated between people with and without herniated intervertebral lumbar discs, volunteers (N = 40) who were diagnosed as having a herniated lumbar disc were compared to control subjects (N = 40) who had been randomly selected and matched by age and sex. All subjects completed a questionnaire to determine the history of their back injury and a description of their exercise behavior patterns. Body composition was estimated by hydrostatic weighing. Maximum oxygen consumption was predicted using the Astrand-Ryhming nomogram. Strength scores were determined from a battery of cable tensiometer tests. Dependent variables were analyzed using a multiple analysis of variance (MANOVA). Using discriminant analysis, as a post hoc test, predicted maximum oxygen consumption was shown to account for the difference between the groups (P less than .002). The control subjects' values were higher than the patients' values. Subjects' exercise history indicated no differences between the groups relative to the time period preceding the onset of injury (P greater than .05). The exercise activity of patients was significantly reduced after injury (P less than .001). An average of 87 days elapsed between the onset of injury to the date of fitness testing.

Adipose Tissue↗

PubMed1988

Isolation of the Drosophila segmentation gene runt and analysis of its expression during embryogenesis.

runt is one of the genes required for establishment of the segmented body pattern of the Drosophila embryo. We have isolated DNA sequences containing this gene using P-element transposon tagging. Southern blot analyses of six different DNA rearrangements that are associated with runt mutations revealed a minimal region of 8.5-kb of DNA that was important for function. In germ line transformation experiments, a 14.5-kb segment of DNA that spanned this minimal region provided significant, although not full, levels of runt activity. The runt gene encoded a 2.6-kb poly(A)+ RNA that underwent a series of dynamic changes in its spatial and temporal patterns of accumulation during embryogenesis. The runt RNA was most abundant at the blastoderm stage when it showed the seven stripes of expression characteristic of other Drosophila pair-rule genes.

Animals↗

PubMed1990

The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system.

Generation of the anterior-posterior body pattern in the Drosophila embryo requires the activity of the segmentation genes. The segmentation gene runt has been classified as one of the primary pair-rule genes because of the pivotal role it plays in regulating the expression of other pair-rule genes. Here, we present the structure of this gene and describe the pattern of runt protein expression during embryogenesis. The deduced protein sequence shows no obvious overall homology with any sequences in the data base. The absence of an identifiable transcription factor motif (e.g., homeo box, zinc finger, leucine zipper, or helix-loop-helix) makes runt different from the other early-acting segmentation proteins. A runt-specific polyclonal antibody was generated and used to demonstrate that the subcellular location of the protein is in the nucleus. Double-staining immunolocalization experiments were used to determine the overlap of the runt protein pattern with the patterns of the pair-rule genes hairy (h), even-skipped (eve), and fushi tarazu (ftz). We found that the patterns of runt and hairy are complementary. Their phasing is shifted anteriorly by two cell diameters with respect to the complementary eve and ftz patterns. Experiments with the runt antibody also indicated that the protein is present throughout embryogenesis and is expressed extensively in the developing central and peripheral nervous system.

Amino Acid Sequence↗

PubMed1992

Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system.

The gap genes of Drosophila are the first zygotic genes to respond to the maternal positional signals and establish the body pattern along the anterior-posterior axis. The gap gene knirps, required for patterning in the posterior region of the embryo, can be activated throughout the wild-type embryo and is normally repressed from the anterior and posterior sides. These results provide direct molecular evidence that the posterior morphogen system interacts in a fundamentally different manner than do hunchback and bicoid, which are responsible for anterior pattern formation.

Animals↗

PubMed1988

Anterior determinants in embryos of Chironomus samoensis: characterization by rescue bioassay.

Embryos of Chironomus samoensis are programmed, by anterior u.v. irradiation, to form the abnormal body pattern 'double abdomen'. Most double abdomen embryos show a mirror-image duplication of abdominal segments in the absence of cephalic or thoracic segments. Such embryos can be 'rescued', i.e. restored to normal development, by microinjection of cytoplasm or RNA from unirradiated donor embryos. Most of the rescued embryos look completely normal and many of them hatch spontaneously. The rescuing activity decreases from the anterior to the posterior pole in the donor cytoplasm and must be delivered near the anterior pole of the recipient for maximum efficiency. Rescuing activity is present in total RNA extracted from whole, unirradiated embryos. Upon fractionation, the activity is associated with poly(A)+ RNA, with LiCl precipitate depleted of RNA smaller than 250 nucleotides (nt) and with a sucrose gradient fraction depleted of RNA larger than 500 nt. Corresponding fractions of RNA from Xenopus oocytes have no rescuing activity. The activity of Chironomus RNA is sensitive to u.v. irradiation with low fluence affecting less than 2% of the pyrimidine bases. Rescuing activity is present in cytoplasm until the blastoderm stage but disappears earlier from poly(A)+ RNA. Rescuing activity is also present, and localized, in cytoplasm of embryos from two related dipterans, Smittia sp. and Drosophila melanogaster, although the extent of rescue observed in Chironomus decreases with the phylogenetic distance between donor and recipient. The results of these and previous experiments indicate that dipteran embryos contain localized RNP particles acting as anterior determinants. In Chironomus, the activity of these particles seems to depend on the integrity of polyadenylated RNA of about 250 to 500 nt length.

Abdomen↗

PubMed1989

Potentiation by the lithium ion of morphogenetic responses to a Xenopus inducing factor.

We have cultured explants of Xenopus blastular animal cap tissue from embryos that had received an earlier treatment with LiCl and from their untreated siblings, in various concentrations of XTC-cell-derived mesoderm-inducing factor (XTC-MIF, Smith, 1987; Smith et al. 1988). The pretreatment with lithium that we used transforms later morphogenesis in the whole embryo to give radialized body forms with anterior/dorsal levels of structure grossly over-represented. In addition, animal caps from 'Li+' embryos were allowed to develop without exposure to in vitro MIF (Li+ controls) and compared with normal uninduced control explants, and explants were made from normal early blastulae but given various initial treatments with LiCl in culture. The results confirm that the lithium ion itself will not induce mesoderm in competent, animal cap tissue of Xenopus. It does, however, enhance the responsiveness of this tissue to XTC-MIF, in a way that parallels its recently reported effect in the case of another mesoderm inducer of different character, bFGF (Slack et al. 1988). The effects observed are sufficient to imply that the altered body pattern that follows lithium treatment, in whole embryos, could be caused by modulation of the responses to an unaltered pattern of in situ inductive stimuli. We also observe evidence that appreciable inductive signals reach animal pole tissue beyond the limits of mesoderm formation in normal development. Relatively low concentrations of MIF prevent the development of an epidermis-specific marker in dissociated blastular animal cap cells (Symes et al. 1988). When such experiments are repeated in relation to the lithium pretreatment of embryos, such treatment is seen to have sensitized the cell population, so that the MIF concentration range that assures complete suppression of the marker is reduced. The results are discussed in relation to induction considered as pattern formation.

Animals↗

PubMed1990

The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

Mesoderm in Xenopus and other amphibian embryos is induced by signals from the vegetal hemisphere acting on equatorial or animal hemisphere cells. These signals are diffusible and two classes of candidate signal molecule have been identified: the fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) types. In this paper, we compare the effects of cloned Xenopus basic FGF (XbFGF) and electophoretically homogeneous XTC-MIF (a TGF-beta-like factor obtained from a Xenopus cell line) on animal pole explants. We find that they have a similar minimum active concentration (0.1-0.2 ng ml-1) but that, nonetheless, XTC-MIF is at least 40 times more active in inducing muscle. In general, we find that the two factors cause inductions of significantly different characters in terms of tissue type, morphology, gene expression and timing. At low concentrations (0.1-1.0 ng ml-1) both factors induce the differentiation of 'mesenchyme' and 'mesothelium' as well as blood-like cells. These latter cells do not, however, react with an antibody to Xenopus globin. This raised the possibility that the identification of red blood cells in other studies on mesoderm induction might have been mistaken, but combinations of animal pole regions with ventral vegetal pole regions confirmed that genuine erythrocytes are formed. The identity of the blood-like cells formed in response to the inducing factors remains unknown. At higher concentrations XTC-MIF induces neural tissue, notochord, pronephros and substantial and often segmented muscle. By contrast, XbFGF only induces significant amounts of muscle above 24 ng ml-1 and even then this is much less than that induced by XTC-MIF. For both factors an exposure of less than 30 min is effective. Competence of animal pole cells to respond to XbFGF is completely lost by the beginning of gastrulation (stage 10) while competence to XTC-MIF is detectable until somewhat later (stage 11). Since animal pole tissue is known to be able to respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

Animals↗

PubMed1992

Transcriptional control by Drosophila gap genes.

The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region-specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair-rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior-posterior axis of the embryo: maternal transcription factors regulate the region-specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva.

Animals↗

PubMed1990

[Association of lichen planus and discoid lupus erythematosus. A clinical and histopathological study of 2 cases].

Two patients showing features of both lichen planus and lupus erythematosus are described: reticular whitish patches in the oral mucosa coexisting with chronic, partly atrophic LED-like skin lesions located on the face were present in both of them. The histological, histochemical and immunopathological findings allowed to diagnose a "LP-LE coexistence" more than a mixed LP-LE disease. The clinical, histological and immunological relationships between LP and LE are discussed and it is suggested that the pathogenesis of the coexistence of the two diseases could be related to a common pathophysiological pathway. It might be that LP and LE are due to a single aetiological agent (e.g. a virus) interacting with different genetic backgrounds to cause LE in some, LP in others and an intermediate disease in a small group of patients. The histopathological and immunopathological features that distinguish LP from LE are the concentration of lymphocytes in areas of keratinocyte damage, the different colloid bodies patterns and the direct IF findings. The Authors conclude that further studies should be performed on "LP-LE coexistence".

Adult↗

PubMed1990

[Urinary incontinence and prolapse. Medical treatment and functional treatment].

Urinary continence implies that the variations of the vesical pressure does not exceed the capacities of the cervico-urethral closure system. The aim of the various methods of treatment is to have a beneficial action on those two parameters: drug therapy will mainly reduce the intra-vesical pressure (parasympatholytics...) and also improve the urethral tone (alpha-adrenergics...), or have a mixed effect on both systems (tricyclic antidepressants, oestrogens...). The side effects are often numerous due to the impact on the vegetative or neuromuscular system. The re-education is complemented by: local and general kinesitherapy, sensorial retrocontrol, associated or not to electrotherapy. Motivation and active participation of the patient are essential. The indications covers all the various pathologies (perineal insufficiency, defects in the body pattern, prolapse, sphincteral insufficiency, transmission problems, vesical instability, urethral instability) and concerns patients of all age groups.

Biofeedback, Psychology↗

PubMed1988

Subtypes in major depression without melancholia.

Using the Diagnostic and Statistical Manual of Mental Disorders (DSM III, 1980) criteria to diagnose major depression without melancholia, 70 adult patients were selected for further detailed clinical and neuro-endocrinological evaluation. Two subtypes emerged; changes in sleeping patterns, body mass and thyrotrophin response to thyrotrophin-releasing hormone constituted the distinguishing features between the two categories (P = 0.012).

Adult↗