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At least 235 records · Page 13Linked to original sources
PubMed1998

Anterior patterning in mouse.

The anteroposterior axis of the vertebrate embryo becomes explicit during gastrulation, the process that converts a relatively featureless embryonic precursor population into new tissues assembled into a recognisable body pattern. Vertebrate embryos arrive at gastrulation in very different states in terms of their size, cell number and reliance on factors inherited from the unfertilized egg. However, they emerge from gastrulation looking very similar, and there is now extensive molecular genetic evidence to indicate that the bare essentials of the gastrulation process have been well conserved during evolution. Here, we review recent findings in the mouse that suggest that anterior identity is, in fact, established before gastrulation starts. They suggest that it is first manifest in extraembryonic tissue and that this tissue is essential for the embryo to develop normal anterior structures, such as the forebrain. We also argue that this precocious anterior pattern could have a counterpart in other non-mammalian vertebrates.

Animals↗
PubMed1999

[Segmentation in vertebrates: a molecular clock linked to periodic somite formation].

In the vertebrate embryo, somites constitute the basis of the segmental body pattern. They give rise to the axial skeleton, the dermis of the back and all striated muscles of the body. In the chick embryo, a pair of somites buds off, in a highly coordinated fashion, every 90 minutes, from the cranial end of the presomitic mesoderm (PSM) while new mesenchymal cells enter the paraxial mesoderm as a consequence of gastrulation. The processes leading to the segmentation of the somite are not yet understood. We have identified and characterised c-hairy1, an avian homologue of the Drosophila segmentation gene, hairy. c-hairy1 is strongly expressed in the presomitic mesoderm where its mRNA exhibits a cyclic posterior-to-anterior wave of expression whose periodicity corresponds to the formation time of one somite (90 min). Fate mapping of the rostral half of the PSM using the quail-chick chimera technique supports a model of cryptic segmentation within the presomitic mesoderm, and indicates that c-hairy1 expression dynamics are not due to massive cell displacement. Analysis of in vitro cultures of isolated presomitic mesoderm demonstrates that rhythmic c-hairy1 mRNA production and degradation is an autonomous property of the paraxial mesoderm. Rather than resulting from the caudal-to-rostral propagation of an activating signal, it arises from pulses of c-hairy1 expression that are coordinated in time and space. Blocking protein synthesis does not alter the propagation of c-hairy1 expression, indicating that negative autoregulation of c-hairy1 expression is unlikely to control its periodic expression. Most of the segmentation models proposed for somite formation rely on the existence of an internal clock coordinating the cells to segment together to form a somite. These results provide the first molecular evidence of a developmental clock linked to segmentation and somitogenesis of the paraxial mesoderm, and support the possibility that segmentation mechanisms used by invertebrates and vertebrates have been conserved.

Animals↗
PubMed1999

Spatially regulated translation in embryos: asymmetric expression of maternal Wnt-11 along the dorsal-ventral axis in Xenopus.

Transition from symmetry to asymmetry is a central theme in cell and developmental biology. In Xenopus embryos, dorsal-ventral asymmetry is initiated by a microtubule-dependent cytoplasmic rotation during the first cell cycle after fertilization. Here we show that the cytoplasmic rotation initiates differential cytoplasmic polyadenylation of maternal Xwnt-11 RNA, encoding a member of the Wnt family of cell-cell signaling factors. Translational regulation of Xwnt-11 mRNA along the dorsal-ventral axis results in asymmetric accumulation of Xwnt-11 protein. These results demonstrate spatially regulated translation of a maternal cell-signaling factor along the vertebrate dorsal-ventral axis and represent a novel mechanism for Wnt gene regulation. Spatial regulation of maternal RNA translation, which has been established in invertebrates, appears to be an evolutionarily conserved mechanism in the generation of intracellular asymmetry and the consequential formation of the multicellular body pattern.

Animals↗
PubMed2001

A two-factor model of disordered eating.

General psychopathology (i.e., personality disturbance, mood/affect dysregulation) has been identified as common and perhaps etiologically important in eating disorder (ED) patients. In this context, we examined a two-factor model of disordered eating which implicated the independent and interactive contribution of (a) general psychopathology (personality) and (b) eating-related psychopathology (body esteem) in explaining deviant eating patterns. A sample of 266 female college/university students (M age=22.1) and 76 women with a clinically diagnosed ED (M age=28.09) completed paper and pencil questionnaires of deviant eating patterns, body esteem, and personality pathology. First, a K-means cluster procedure revealed a compelling three-cluster solution among the nonclinical women based on deviant eating variables: < >(n=61), < > (n=92), and < > (n=103). The ED women were classified as Cluster 4; < > (n=76). Second, to evaluate our two-factor model, multinomial logistic regression (MLR) was used with cluster membership as the outcome variable and the following variables as predictors: body esteem, personality pathology, and all two-way interactions. In addition to several significant main effects, three interaction terms were marginally significant: Body esteem appearance x Narcissism (P=.047), Body esteem weight x Narcissism (P=.044), and Body esteem attribution x Stimulus seeking(P=.051). The overall extent of correct cluster classification was 63%. These results indicate that the presence of both low body esteem and maladaptive personality, and the interactive operation of these two factors, seems to contribute to the likelihood of having an eating disorder, beyond the independent contribution of either factor alone. Results are considered in the context of etiological models in which general psychopathology presents a vulnerability factor in ED development.

Journal Article↗
PubMed2004

Computational identification of microRNA targets.

Recent experiments have shown that the genomes of organisms such as worm, fly, human, and mouse encode hundreds of microRNA genes. Many of these microRNAs are thought to regulate the translational expression of other genes by binding to partially complementary sites in messenger RNAs. Phenotypic and expression analysis suggests an important role of microRNAs during development. Therefore, it is of fundamental importance to identify microRNA targets. However, no experimental or computational high-throughput method for target site identification in animals has been published yet. Our main result is a new computational method that is designed to identify microRNA target sites. This method recovers with high specificity known microRNA target sites that have previously been defined experimentally. Based on these results, we present a simple model for the mechanism of microRNA target site recognition. Our model incorporates both kinetic and thermodynamic components of target recognition. When we applied our method to a set of 74 Drosophila melanogaster microRNAs, searching 3'UTR sequences of a predefined set of fly mRNAs for target sites which were evolutionary conserved between D. melanogaster and Drosophila pseudoobscura, we found that many key developmental body patterning genes such as hairy and fushi-tarazu are likely to be translationally regulated by microRNAs.

Algorithms↗
PubMed1987

Fat patterning in Papua New Guineans: effects of age, sex and acculturation.

For the renewed interest in fat patterning to be fruitful, more information on the biology of fat patterning, particularly normative data are required. Nine skinfold thicknesses were measured in 2312 coastal and highland Papua New Guineans of all ages undergoing acculturation. Principal component analysis of the skinfold data revealed components of fatness and fat patterning. First component scores were typical of the changes in fatness with age and the sex differences expected in these populations. Second component scores of limb-trunk fat patterning showed marked changes with age in both sexes but they stabilised in adulthood. This pattern seemed more affected by maturity although it is usually thought to be a sex-specific pattern. The third component, upper-lower body patterning, was more sexually dimorphic in adults. Marked differences were not observed between the two communities but over a 15-year period fatness levels increased slightly and subcutaneous fat tended to be deposited more centrally.

Acculturation↗
PubMed2004

Translational control: a cup half full.

Repression of translation of oskar and nanos mRNAs prior to their posterior localization in the egg and embryo is essential for body patterning in Drosophila. The Cup protein is now found to have an important role in repression of both mRNAs, and apparently does so in a manner similar to the action of the Xenopus Maskin protein.

Animals↗
PubMed2002

beta-Catenin in early development of the lancelet embryo indicates specific determination of embryonic polarity.

The lancelet (amphioxus) embryo develops from a miolecithal egg and starts gastrulation when it is approximately 400 cells in size, in a fashion similar to that of some non-chordate deuterostomes. Throughout this type of gastrulation, the embryo develops characteristics such as the notochord and hollow nerve cord that commonly appear in chordates. beta-Catenin is an important factor in initiating body patterning. The behavior and developmental pattern of this protein in early lancelet development was examined in this study. Cytoplasmic beta-catenin was localized to the animal pole after fertilization and then was incorporated asymmetrically into the blastomeres during the first cleavage. Asymmetric distribution was observed at least until the 32-cell stage. The first nuclear localization was at the 64-cell stage, and involved all of the cells. At the initial gastrula stage, however, concentrated beta-catenin was found on the dorsal side. LiCl treatment affected the asymmetric pattern of beta-catenin during the first cleavage. LiCl also changed distribution of nuclear beta-catenin at the initial gastrula stage: distribution extended to cells on the animal side. Apparently associated with this change, expression domains of goosecoid, lhx3 and otx also changed to a radially symmetric pattern centered at the animal pole. However, LiCl-treated embryos were able to establish embryonic polarity. The present study suggests that in the lancelet embryo, polarity determination is independent of dorsal morphogenesis.

Animals↗
PubMed2001

Ancient origin of the Hox gene cluster.

The Hox gene cluster has a crucial function in body patterning during animal development. How and when this gene cluster originated is being clarified by recent data from Cnidaria, a basal animal phylum. The characterization of Hox-like genes from Hydra, sea anemones and jellyfish has revealed that a Hox gene cluster is extremely ancient, having originated even before the divergence of these basal animals.

Animals↗
PubMed2006

Wnt/beta-catenin signaling and body plan formation in mouse embryos.

Wnt/beta-catenin signaling plays fundamental roles in body patterning in many invertebrate and vertebrate species, by acting as a key regulator of germ layer and body axis specification. This article focuses on the roles of Wnt/beta-catenin signaling in mouse early embryos, which exhibit a unique mode of development compared to non-mammalian vertebrates. Current experimental evidence suggests that Wnt/beta-catenin signaling is not essential for patterning embryos before implantation. However, Wnt/beta-catenin signaling regulates critical developmental events after implantation, namely the patterning of visceral endoderm, the induction of primitive streak, and the formation of anterior neural ectoderm. While Wnt/beta-catenin signaling regulates the body axis formation in both mouse and frog, the mode of its action is significantly diverged between these two vertebrate species.

Animals↗
PubMed2003

Recognition of a bicoid mRNA localization signal by a protein complex containing Swallow, Nod, and RNA binding proteins.

Localization of mRNAs, a process essential for embryonic body patterning in Drosophila, requires recognition of cis-acting signals by cellular components responsible for movement and anchoring. We have purified a large multiprotein complex that binds a minimal form of the bicoid mRNA localization signal in a manner both specific and sensitive to inactivating mutations. Identified complex components include the RNA binding proteins Modulo, PABP, and Smooth, the known localization factor Swallow, and the kinesin family member Nod. We demonstrate that localization of bcd mRNA is defective in modulo mutants. The presence of three required localization components (Swallow, Modulo, and specific RNA binding activity) within the recognition complex strongly implicates it in mRNA localization.

Animals↗
PubMed1989

The egg came first, of course! Anterior-posterior pattern formation in Drosophila embryogenesis and oogenesis.

The anterior-posterior body pattern of the Drosophila embryo is initiated through the action of maternal gene products. In particular, three groups of maternally acting genes (the anterior, posterior and terminal groups) have been shown to direct the synthesis and spatial restriction of the three major organizing activities in the egg. The initial spatial localizations of the maternal organizing activities are established during oogenesis. After fertilization these activities regulate zygotic gene activity along the anterior-posterior axis of the egg.

Animals↗
PubMed2006

The yolk syncytial layer regulates myocardial migration by influencing extracellular matrix assembly in zebrafish.

The roles of extra-embryonic tissues in early vertebrate body patterning have been extensively studied, yet we know little about their function during later developmental events. Here, we analyze the function of the zebrafish extra-embryonic yolk syncytial layer (YSL) specific transcription factor, Mtx1, and find that it plays an essential role in myocardial migration. Downregulating the function of Mtx1 in the YSL leads to cardia bifida, a phenotype in which the myocardial cells fail to migrate to the midline. Mtx1 in the extra-embryonic YSL appears to regulate the embryonic expression of fibronectin, a gene previously implicated in myocardial migration. We further show dosage-sensitive genetic interactions between mtx1 and fibronectin. Based on these data, we propose that the extra-embryonic YSL regulates myocardial migration, at least in part by influencing fibronectin expression and subsequent assembly of the extracellular matrix in embryonic tissues.

Animals↗
PubMed2003

Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient.

Morphogen gradients control body pattern by differentially regulating cellular behavior. Here, we analyze the molecular events underlying the primary response to the Dpp/BMP morphogen in Drosophila. Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene. We first provide significance for the brk expression gradient by showing that different Brk levels repress distinct combinations of wing genes expressed at different distances from Dpp-secreting cells. We then dissect the brk regulatory region and identify two separable elements with opposite properties, a constitutive enhancer and a Dpp morphogen-regulated silencer. Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri. Together, our results provide the molecular framework for a mechanism by which the extracellular Dpp/BMP morphogen establishes a finely tuned, graded read-out of transcriptional repression.

Amino Acid Sequence↗
PubMed1999

The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene.

The Drosophila gene bicoid functions as the anterior body pattern organizer of Drosophila. Embryos lacking maternally expressed bicoid fail to develop anterior segments including head and thorax. In wild-type eggs, bicoid mRNA is localized in the anterior pole region and the bicoid protein forms an anterior-to-posterior concentration gradient. bicoid activity is required for transcriptional activation of zygotic segmentation genes and the translational suppression of uniformly distributed maternal caudal mRNA in the anterior region of the embryo. caudal genes as well as other homeobox genes or members of the Drosophila segmentation gene cascade have been found to be conserved in animal evolution. In contrast, bicoid homologs have been identified only in close relatives of the schizophoran fly Drosophila. This poses the question of how the bicoid gene evolved and adopted its unique function in organizing anterior-posterior polarity. We have cloned bicoid from a basal cyclorrhaphan fly, Megaselia abdita (Phoridae, Aschiza), and show that the gene originated from a recent duplication of the direct homolog of the vertebrate gene Hox3, termed zerknüllt, which specifies extraembryonic tissues in insects.

Amino Acid Sequence↗
PubMed1997

GATA4 transcription factor is required for ventral morphogenesis and heart tube formation.

Previous studies have suggested that the GATA4 transcription factor plays an important role in regulating mammalian cardiac development. In the studies described in this report we have used gene targeting to produce GATA4-deficient mice. Homozygous GATA4-deficient (GATA4-/-) mice died between 8.5 and 10.5 days post coitum (dpc). GATA4-/- embryos displayed severe defects in both rostral-to-caudal and lateral-to-ventral folding, which were reflected in a generalized disruption of the ventral body pattern. This resulted in the defective formation of an organized foregut and anterior intestinal pore, the failure to close both the amniotic cavity and yolk sac, and the uniform lack of a ventral pericardial cavity and heart tube. Analysis of cardiac development in the GATA4-/- mice demonstrated that these embryos developed splanchnic mesoderm, which differentiated into primitive cardiac myocytes that expressed contractile proteins. However, consistent with the observed defect in ventral morphogenesis, these GATA4-/- procardiomyocytes failed to migrate to the ventral midline to form a linear heart tube and instead formed aberrant cardiac structures in the anterior and dorsolateral regions of the embryo. The defect in ventral migration of the GATA4-/- procardiomyocytes was not cell intrinsic because GATA4-/- cardiac myocytes and endocardial cells populated the hearts of GATA4-/- -C57BL/6 chimeric mice. Taken together, these results demonstrated that GATA4 is not essential for the specification of the cardiac cell lineages. However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis.

Animals↗
PubMed2004

Cellular expression of eve1 suggests its requirement for the differentiation of the ameloblasts and for the initiation and morphogenesis of the first tooth in the zebrafish (Danio rerio).

even-skipped-related (evx) genes encode homeodomain-containing transcription factors that are involved in a series of developmental processes such as posterior body patterning and neurodifferentiation. Although evx1 and evx2 were not reported to be expressed during mammalian tooth development, we present here evidence that eve1, the closest paralog of evx1 in the actinopterygian lineage, is expressed during pharyngeal tooth formation in the zebrafish, Danio rerio. We have performed whole-mount in situ hybridization on zebrafish embryos and larvae ranging from 24 to 192 hours postfertilization (hpf). A detailed analysis of serial sections through the pharyngeal region of whole-mount hybridized and control specimens indicates that only dental epithelial cells express eve1. eve1 transcription was activated at 48 hpf, in the placode of the first tooth (i.e., the initiation site of tooth 4V(1)), and maintained in the dental epithelium throughout morphogenesis. Then, by 72 hpf, eve1 expression was restricted to the differentiating ameloblasts of the enamel organ during early differentiation stage, and this expression decreased as soon as matrix was deposited. In subsequent primary teeth (3 V(1) and 5 V(1)) as well as in their successors (replacement teeth 4V(2), 3V(2), and 5V(2)), eve1 expression was restricted to the differentiating ameloblasts and, again, disappeared when matrix was deposited. Therefore, in the zebrafish, eve1 expression in the pharyngeal region is correlated with two key steps of tooth development: initiation and morphogenesis of the first tooth, and ameloblast differentiation of all developing teeth.

Adaptor Proteins, Signal Transducing↗
PubMed1990

Changes in antepartum heart rate patterns with progressive deterioration of the fetal condition.

In this paper changes in antepartum fetal heart rate (FHR) patterns are described, that occur with progressive deterioration of the fetal condition. The data on the relationship between heart rate patterns and fetal blood gas and pH values are reviewed. A possible rank ordering is presented in which changes in FHR pattern, body movements and blood flow velocity wave form patterns occur with progressive deterioration of the fetal condition. It is concluded that in small-for-date fetuses changes in heart rate and movement patterns are rather late signs of impairment, coinciding with fetal hypoxaemia. In general, heart rate variation falls below the norm at the same time as decelerations occur; there are, however, large inter-fetal differences. In general, abnormal Doppler velocity wave form patterns precede the occurrence of heart rate decelerations. Their impact on the timing of delivery is, however, still uncertain. The advantages of a numerical analysis of FHR patterns include identification of fetuses with low FHR variation, precision of the actual fetal condition and (at early gestation) longitudinal follow-up of fetuses with abnormal heart rate patterns.

Animals↗