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PubMed1993

Insulin and androgen relationships with abdominal body fat distribution in women with and without hyperandrogenism.

This retrospective study was carried out to investigate, in a large group of hyperandrogenized women with polycystic ovary syndrome (PCOS) and nonhyperandrogenized control women, the interrelationships between sex steroids and indices of body fat distribution. Moreover, we investigated the relationships between these parameters and insulin blood levels, since obese women with abdominal pattern of fat distribution (A-BFD), as well as those with PCOS (either obese and nonobese) are characterized by moderate to severe hyperinsulinemia. A sample of 100 women with PCOS and that of 138 women without clinical signs of hyperandrogenism, who served as a control group, were investigated. The waist to hip circumference ratio (WHR) which was used to define different patterns of fat topography was significantly (p < 0.05) higher in PCOS (0.84 +/- 0.10) than in control women (0.81 +/- 0.08). In both groups, women with WHR values lower than or equal to 0.85 were considered as having a peripheral pattern of body fat distribution (P-BFD) whereas those having WHR values higher than 0.85 had A-BFD. Compared to controls, women with PCOS had higher LH, androgen and estrogen concentrations. In both PCOS and controls there were no differences in sex hormone levels between women with different patterns of fat distribution, except androstenedione, which levels were significantly higher in women with A-BFD than with P-BFD. Women with PCOS showed significantly higher insulin levels than controls. Moreover, in both groups fasting and stimulated insulin were significantly higher in women with A-BFD than in those with P-BFD.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed2000

Somite formation and patterning.

As a consequence of their segmented arrangement and the diversity of their tissue derivatives, somites are key elements in the establishment of the metameric body plan in vertebrates. This article aims to largely review what is known about somite development, from the initial stages of somite formation through the process of somite regionalization along the three major body axes. The role of both cell intrinsic mechanisms and environmental cues are evaluated. The periodic and bilaterally synchronous nature of somite formation is proposed to rely on the existence of a developmental clock. Molecular mechanisms underlying these events are reported. The importance of an antero-posterior somitic polarity with respect to somite formation on one hand and body segmentation on the other hand is discussed. Finally, the mechanisms leading to the regionalization of somites along the dorso-ventral and medio-lateral axes are reviewed. This somitic compartmentalization is believed to underlie the segregation of dermis, skeleton, and dorsal and appendicular musculature.

Animals↗
PubMed1999

Cell lineage analysis of pattern formation in the Tubifex embryo. I. Segmentation in the mesoderm.

Annelids are strongly segmented animals that display a high degree of metamerism in their body plan. The embryonic origin of metameric segmentation was examined in an oligochaete annelid Tubifex using lineage tracers. Segmental organization arises sequentially in the anterior-to-posterior direction along the longitudinal axis of the mesodermal germ band, a coherent column of primary blast cells that are produced from the mesodermal teloblast. Shortly after its birth, each primary blast cell undergoes a spatiotemporally stereotyped sequence of cell divisions to generate three classes of cells (in terms of cell size), which together give rise to a distinct cell cluster. Each cluster is composed of descendants of a single primary blast cell; there is no intermingling of cells between adjacent clusters. Relatively small-sized cells in each cluster become localized at its periphery, and they form coelomic walls including an intersegmental septum to establish individuality of segments. A set of cell ablation experiments showed that these features of mesodermal segmentation are not affected by the absence of the overlying ectodermal germ band. These results suggest that each primary blast cell serves as a founder cell of each mesodermal segment and that the boundary between segments is determined autonomously. It is concluded that the metameric body plan of Tubifex arises from an initially simple organization (i.e., a linear series) of segmental founder cells.

Animals↗
PubMed1975

Clinical aspects of the disruptive effects of road accidents on the human body.

Knowledge of the patterns of injury from road accidents helps to reduce the risk of diagnostic error through oversight. Understanding the patterns of disruption of the body gives surgeons a better understanding of the nature of the injury and of the behaviour of the injuried tissues. This is of particular value in the diagnostic manipulation of fractures to decide whether they need internal fixation or whether external splintage will keep them in an acceptable position.

Accidents, Traffic↗
PubMed1999

Expression patterns of threespine stickleback hox genes and insights into the evolution of the vertebrate body axis.

Understanding the patterning mechanisms that operate to promote differentiation of individual segments along the main body axis is an important goal of both developmental and evolutionary biology. In order to gain a better insight into the role of Hox genes in generating diversity of axial plans seen in vertebrates, we have cloned 11 homeobox sequences from an acanthopterygian teleost, the threespine stickleback, and analyzed the expression of 7 of these during embryogenesis. Transcripts are observed in a variety of tissues, including the neural tube, paraxial mesoderm, lateral plate mesoderm, pectoral fins, pronephric ducts, as well as some neural crest-derived structures. Anterior limits of expression in the central nervous system and paraxial mesoderm exhibited both similarities and differences to those of mouse and zebrafish homologs. In both stickleback and zebrafish embryos expression limits within the paraxial mesoderm were detected only within the trunk region in which ribs are attached to all vertebrae. The finding of this pattern in two divergent teleosts as well as in various tetrapod species supports the hypothesis that a Hox precode was present prior to the divergence of ray-finned and lobe-finned fishes and was subsequently used to generate different types of vertebrae in tetrapods. We also describe a dynamic pattern of expression of several stickleback Hox genes associated with the development of the caudal paraxial mesoderm, which suggests uncoupling of the process of segmentation from segmental identity determination. We propose that in fishes the patterning of the tail region is under the control of a separate mechanism from the trunk, which utilizes Hox genes in a different manner.

Amino Acid Sequence↗
PubMed1996

Disordered eating and its psychosocial correlates among Chinese adolescent females in Hong Kong.

OBJECTIVES: To study the prevalence of disordered eating and its relationship with body dissatisfaction, family dysfunction, and depression among Chinese adolescent females in Hong Kong. METHOD: Two hundred ninety-four schoolgirls completed a demographic and weight history sheet, Eating Attitudes Test-26, Body Dissatisfaction Scale, cohesion and conflict subscales of the Family Environment Scale, and the Beck Depression Inventory. RESULTS: 6.5% of subjects were EAT-26 high scores. Disordered eating was positively predicted by body dissatisfaction and, to a lesser extent, family cohesion and conflict. Body dissatisfaction was in turn positively predicted by depression, which was negatively predicted by family cohesion. DISCUSSION: Western patterns of body dissatisfaction and disordered eating attitudes are common among Chinese adolescent females. In the presence of psychosocial vulnerability factors, more weight control behavior and eating disorders may be expected to arise in Hong Kong.

Adolescent↗
PubMed1998

Screening mosaic F1 females for mutations affecting zebrafish heart induction and patterning.

The genetic pathways underlying the induction and anterior-posterior patterning of the heart are poorly understood. The recent emergence of the zebrafish model system now allows a classical genetic approach to such challenging problems in vertebrate development. Two large-scale screens for mutations affecting zebrafish embryonic development have recently been completed; among the hundreds of mutations identified were several that affect specific aspects of cardiac morphogenesis, differentiation, and function. However, very few mutations affecting induction and/or anterior-posterior patterning of the heart were identified. We hypothesize that a directed approach utilizing molecular markers to examine these particular steps of heart development will uncover additional such mutations. To test this hypothesis, we are conducting two parallel screens for mutations that affect either the induction or the anterior-posterior patterning of the zebrafish heart. As an indicator of cardiac induction, we examine expression of nkx2.5, the earliest known marker of precardiac mesoderm; to assess anterior-posterior patterning, we distinguish ventricle from atrium with antibodies that recognize different myosin heavy chain isoforms. In order to expedite the examination of a large number of mutations, we are screening the haploid progeny of mosaic F1 females. In these ongoing screens, we have identified four mutations that affect nkx2.5 expression as well as 21 that disrupt either ventricular or atrial development and thus far have recovered several of these mutations, demonstrating the value of our approach. Future analysis of these and other cardiac mutations will provide further insight into the processes of induction and anterior-posterior patterning of the heart.

Animals↗
PubMed2001

Cardiac patterning and morphogenesis in zebrafish.

Development of the embryonic vertebrate heart requires the precise coordination of pattern formation and cell movement. Taking advantage of the availability of zebrafish mutations that disrupt cardiogenesis, several groups have identified key regulators of specific aspects of cardiac patterning and morphogenesis. Several genes, including gata5, fgf8, bmp2b, one-eyed pinhead, and hand2, have been shown to be relevant to the patterning events that regulate myocardial differentiation. Studies of mutants with morphogenetic defects have indicated at least six genes that are essential for cardiac fusion and heart tube assembly, including casanova, bonnie and clyde, gata5, one-eyed pinhead, hand2, miles apart, and heart and soul. Furthermore, analysis of the jekyll gene has indicated its important role during the morphogenesis of the atrioventricular valve. Altogether, these data provide a substantial foundation for future investigations of cardiac patterning, cardiac morphogenesis, and the relationship between these processes.

Animals↗
PubMed2006

Retinoids and nonvertebrate chordate development.

Retinoic acid (RA) is required for the differentiation and morphogenesis of chordate-specific features, such as the antero-posterior regionalization of the dorsal hollow nerve cord and neural crest cells. RA receptors (RARs) have been reported exclusively in chordates, suggesting that the acquisition of the RAR gene was important for chordate evolution. A scenario is presented here for the establishment of an RAR-mediated developmental regulatory system during the course of chordate evolution. In the common chordate ancestor, RAR came to control the spatial expression pattern of Hox genes in the ectoderm and endoderm along the antero-posterior axis. In these germ layers, RA was required for the differentiation of epidermal sensory neurons and the morphogenesis of pharyngeal gill slits, respectively. As the diffuse epidermal nerve net in the chordate ancestor became centralized to form the dorsal nerve cord, the epidermal Hox expression pattern was carried into the central nervous system. Because the Hox code here came to specify neuronal identity along the antero-posterior axis, RA became inextricably linked to the antero-posterior patterning of the chordate central nervous system.

Animals↗
PubMed2001

How the zebrafish gets its stripes.

The study of vertebrate pigment patterns is a classic and enduring field of developmental biology. Knowledge of pigment pattern development comes from a variety of systems, including avians, mouse, and more recently, the zebrafish (Danio rerio). Recent analyses of the mechanisms underlying the development of the neural crest-derived pigment cell type common to all vertebrates, the melanocyte, have revealed remarkable similarities and several surprising differences between amniotes and zebrafish. Here, we summarize recent advances in the study of melanocyte development in zebrafish, with reference to human, mouse, and avian systems. We first review melanocyte development in zebrafish and mammals, followed by a summary of the molecules known to be required for their development. We then discuss several relatively unaddressed issues in vertebrate pigment pattern development that are being investigated in zebrafish. These include determining the relationships between genetically distinct classes of melanocytes, characterizing and dissecting melanocyte stem cell development, and understanding how pigment cells organize into a patterned tissue. Further analysis of zebrafish pigment pattern mutants as well as new generations of directed mutant screens promise to extend our understanding of pigment pattern morphogenesis.

Animals↗
PubMed2005

Thinking clockwise.

Throughout the Animal Kingdom, the time of embryonic development is maintained and strictly controlled. Each step of the process is successful only when it occurs at the right time and place. This raises the question: how is time controlled during embryonic development? Time control is particularly crucial during embryo segmentation processes, where the number of generated segments, as well as the time of formation of each segment, is extraordinarily constant and specific for each species. Somitogenesis is the process through which the vertebrate presomitic mesoderm is segmented along its anterior-posterior axis into round-shaped masses of epithelial cells, named somites. In the chick embryo, a new pair of somites is formed every 90 min. The discovery that this clock-like precision is dictated by the somitogenesis molecular clock constituted a landmark in the Developmental Biology field. Several genes exhibit cyclic gene expression in the embryo presomitic mesoderm from which the somites arise, presenting a 90 min oscillation period, the time required to form a pair of somites. The combined levels of dynamic gene expression throughout the presomitic mesoderm enable cells to acquire positional information, thus giving them a notion of time. Anterior-posterior patterning of the vertebrate nervous system also involves partition into discrete territories. This is particularly evident in the hindbrain where overt segmentation occurs. Nevertheless, little is known about the segmentation genes and mechanisms that may be involved. This paper intends to describe the molecular clock associated with vertebrate somitogenesis, suggesting that it may be operating in many other patterning processes.

Animals↗
PubMed2006

Bone formation: The nuclear matrix reloaded.

In this issue of Cell, Grosschedl and colleagues (Dobreva et al., 2006) report that the nuclear matrix protein Satb2 represses Hoxa2 expression and acts with other regulatory proteins to promote osteoblast differentiation. This work suggests a molecular mechanism that enables the integration of patterning and differentiation during bone formation.

Animals↗
PubMed2004

Butterfly wing pattern evolution is associated with changes in a Notch/Distal-less temporal pattern formation process.

In butterflies there is a class of "intervein" wing patterns that have lines of symmetry halfway between wing veins. These patterns occur in a range of shapes, including eyespots, ellipses, and midlines, and were proposed to have evolved through developmental shifts along a midline-to-eyespot continuum. Here we show that Notch (N) upregulation, followed by activation of the transcription factor Distal-less (Dll), is an early event in the development of eyespot and intervein midline patterns across multiple species of butterflies. A relationship between eyespot phenotype and N and Dll expression is demonstrated in a loss-of-eyespot mutant in which N and Dll expression is reduced at missing eyespot sites. A phylogenetic comparison of expression time series from eight moth and butterfly species suggests that intervein N and Dll patterns are a derived characteristic of the butterfly lineage. Furthermore, prior to eyespot determination in eyespot-bearing butterflies, N and Dll are transiently expressed in a pattern that resembles ancestral intervein midline patterns. In this study we establish N upregulation as the earliest known event in eyespot determination, demonstrate gene expression associated with intervein midline color patterns, and provide molecular evidence that wing patterns evolved through addition to and truncation of a conserved midline-to-eyespot pattern formation sequence.

Animals↗
PubMed2006

Morphogens: precise outputs from a variable gradient.

The morphogen gradient as a source of embryonic patterning is one of the best accepted concepts in developmental biology. Morphogens can be transcription factors or extracellular signals, but in both cases, they are thought to provide concentration thresholds that position different cell fates within the developing embryo. Several recent papers examine the patterning activities of Drosophila Bicoid, the first known molecular morphogen and reach different conclusions about the patterning power of a single morphogen gradient.

Animals↗
PubMed2003

Zic2 is required for neural crest formation and hindbrain patterning during mouse development.

The Zic genes are the vertebrate homologues of the Drosophila pair rule gene odd-paired. It has been proposed that Zic genes play several roles during neural development including mediolateral segmentation of the neural plate, neural crest induction, and inhibition of neurogenesis. Initially during mouse neural development Zic2 is expressed throughout the neural plate while later on expression in the neurectoderm becomes restricted to the lateral region of the neural plate. A hypomorphic allele of Zic2 has demonstrated that in the mouse Zic2 is required for the timing of neurulation. We have isolated a new allele of Zic2 that behaves as a loss of function allele. Analysis of this mutant reveals two further functions for Zic2 during early neural development. Mutation of Zic2 results in a delay of neural crest production and a decrease in the number of neural crest cells that are produced. These defects are independent of mediolateral segmentation of the neurectoderm and of dorsal neurectoderm proliferation, both of which occur normally in the mutant embryos. Additionally Zic2 is required during hindbrain patterning for the normal development of rhombomeres 3 and 5. This work provides the first genetic evidence that the Zic genes are involved in neural crest production and the first demonstration that Zic2 functions during hindbrain patterning.

Animals↗
PubMed2004

BMP receptor IA is required in the mammalian embryo for endodermal morphogenesis and ectodermal patterning.

BMPRIA is a receptor for bone morphogenetic proteins with high affinity for BMP2 and BMP4. Mouse embryos lacking Bmpr1a fail to gastrulate, complicating studies on the requirements for BMP signaling in germ layer development. Recent work shows that BMP4 produced in extraembryonic tissues initiates gastrulation. Here we use a conditional allele of Bmpr1a to remove BMPRIA only in the epiblast, which gives rise to all embryonic tissues. Resulting embryos are mosaics composed primarily of cells homozygous null for Bmpr1a, interspersed with heterozygous cells. Although mesoderm and endoderm do not form in Bmpr1a null embryos, these tissues are present in the mosaics and are populated with mutant cells. Thus, BMPRIA signaling in the epiblast does not restrict cells to or from any of the germ layers. Cells lacking Bmpr1a also contribute to surface ectoderm; however, from the hindbrain forward, little surface ectoderm forms and the forebrain is enlarged and convoluted. Prechordal plate, early definitive endoderm, and anterior visceral endoderm appear to be expanded, likely due to defective morphogenesis. These data suggest that the enlarged forebrain is caused in part by increased exposure of the ectoderm to signaling sources that promote anterior neural fate. Our results reveal critical roles for BMP signaling in endodermal morphogenesis and ectodermal patterning.

Animals↗
PubMed2004

BMP antagonism by Spemann's organizer regulates rostral-caudal fate of mesoderm.

Recent revisions to the Xenopus fate map challenge the interpretation of previous maps and current models of amphibian axial patterning (Lane, M.C., Smith, W.C., 1999. The origins of primitive blood in Xenopus: implications for axial patterning. Development 126 (3), 423-434.; Lane, M.C., Sheets, M.D., 2000. Designation of the anterior/posterior axis in pregastrula Xenopus laevis. Dev. Biol. 225, 37-58). We determined the rostralmost contributions to both dorsal and ventral mesoderm concomitantly from marginal zone progenitors in stage 6 embryos. Data reveal an unequivocal rostral-to-caudal progression of both dorsal and ventral mesoderm across the pre-gastrula axis historically called the dorsal-ventral axis, and a dorsal-to-ventral progression from animal-to-vegetal in the marginal zone. These findings support the proposed revisions to the fate and axis orientation maps. Most importantly, these results raise questions about the role of the organizer grafts and organizer-derived BMP antagonists in the "induction" of secondary axes. We re-examine both phenomena, and find that organizer grafts and BMP antagonists evoke caudal-to-rostral mesodermal fate transformations, and not ventral-to-dorsal transformations as currently believed. We demonstrate that BMP antagonism evokes a second axis because it stimulates precocious mediolateral intercalation of caudal, dorsal mesoderm. The implications of these findings for models of organizer function in vertebrate axial patterning are discussed.

Animals↗