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At least 1,135 records · Page 63Linked to original sources
PubMed1997

The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm.

Development of the Drosophila central nervous system begins with the delamination of neural and glial precursors, called neuroblasts, from the neuroectoderm. An early and important step in the generation of neural diversity is the specification of individual neuroblasts according to their position. In this study, we describe the genetic analysis of the msh gene which is likely to play a role in this process. The msh/Msx genes are one of the most highly conserved families of homeobox genes. During vertebrate spinal cord development, Msx genes (Msx1-3) are regionally expressed in the dorsal portion of the developing neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal bands that correspond to the dorsal half of the neuroectoderm, and subsequently in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss-of-function mutations led to cell fate alterations of neuroblasts formed in the dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate switch. Conversely, ectopic expression of msh in the entire neuroectoderm severely disrupted the proper development of the midline and ventral neuroblasts. The results provide the first in vivo evidence for the role of the msh/Msx genes in neural development, and support the notion that they may perform phylogenetically conserved functions in the dorsoventral patterning of the neuroectoderm.

Animals↗
PubMed1997

Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing.

Short-range interaction between dorsal and ventral (D and V) cells establishes an organizing center at the DV compartment boundary that controls growth and specifies cell fate along the dorsal-ventral axis of the Drosophila wing. The secreted signaling molecule Wingless (Wg) is expressed by cells at the DV compartment boundary and has been implicated in mediating its long-range patterning activities. Here we show that Wg acts directly, at long range, to define the expression domains of its target genes, Distal-less and vestigial. Expression of the Achaete-scute genes, Distal-less and vestigial at different distances from the DV boundary is controlled by Wg in a concentration-dependent manner. We propose that Wg acts as a morphogen in patterning the D/V axis of the wing.

Animals↗
PubMed1998

Local induction of patterning and programmed cell death in the developing Drosophila retina.

Local cell signaling can pattern the nervous system by directing cell fates, including programmed cell death. In the developing Drosophila retina, programmed cell death is used to remove excess cells between ommatidia. Cell ablation revealed the source and position of signals required for regulating the pattern of programmed cell death among these interommatidial cells. Two types of signals regulate this patterning event. Notch-mediated signals between interommatidial precursors result in removal of unneeded cells. Cone cells and primary pigment cells oppose this signal by supplying a 'life'-promoting activity; evidence is provided that this signal occurs through localized activation of the EGF Receptor/Ras pathway. Together, these signals refine the highly regular pattern observed in the adult retina.

Animals↗
PubMed1998

Patterned epidermal cell death in wild-type and segment polarity mutant Drosophila embryos.

Programmed cell death plays an essential role in the normal embryonic development of Drosophila melanogaster. One region of the embryo where cell death occurs, but has not been studied in detail, is the abdominal epidermis. Because cell death is a fleeting process, we have used time-lapse, fluorescence microscopy to map epidermal apoptosis throughout embryonic development. Cell death occurs in a stereotypically striped pattern near both sides of the segment border and to a lesser extent in the middle of the segment. This map of wild-type cell death was used to determine how cell death patterns change in response to genetic perturbations that affect epidermal patterning. Previous studies have suggested that segment polarity mutant phenotypes are partially the result of increased cell death. Mutations in wingless, armadillo, and gooseberry led to dramatic increases in apoptosis in the anterior of the segment while a naked mutation resulted in a dramatic increase in the death of engrailed cells in the posterior of the segment. These results show that segment polarity gene expression is necessary for the survival of specific rows of epidermal cells and may provide insight into the establishment of the wild-type epidermal cell death pattern.

Animals↗
PubMed2000

bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish.

In vertebrate embryos, maternal (beta)-catenin protein activates the expression of zygotic genes that establish the dorsal axial structures. Among the zygotically acting genes with key roles in the specification of dorsal axial structures are the homeobox gene bozozok (boz) and the nodal-related (TGF-(beta) family) gene squint (sqt). Both genes are expressed in the dorsal yolk syncytial layer, a source of dorsal mesoderm inducing signals, and mutational analysis has indicated that boz and sqt are required for dorsal mesoderm development. Here we examine the regulatory interactions among boz, sqt and a second nodal-related gene, cyclops (cyc). Three lines of evidence indicate that boz and sqt act in parallel to specify dorsal mesoderm and anterior neuroectoderm. First, boz requires sqt function to induce high levels of ectopic dorsal mesoderm, consistent with sqt acting either downstream or in parallel to boz. Second, sqt mRNA is expressed in blastula stage boz mutants, indicating that boz is not essential for activation of sqt transcription, and conversely, boz mRNA is expressed in blastula stage sqt mutants. Third, boz;sqt double mutants have a much more severe phenotype than boz and sqt single mutants. Double mutants consistently lack the anterior neural tube and axial mesoderm, and ventral fates are markedly expanded. Expression of chordin and noggin1 is greatly reduced in boz;sqt mutants, indicating that the boz and sqt pathways have overlapping roles in activating secreted BMP antagonists. In striking contrast to boz;sqt double mutants, anterior neural fates are specified in boz;sqt;cyc triple mutants. This indicates that cyc represses anterior neural development, and that boz and sqt counteract this repressive function. Our results support a model in which boz and sqt act in parallel to induce dorsalizing BMP-antagonists and to counteract the repressive function of cyc in neural patterning.

Animals↗
PubMed2000

Endoderm patterning by the notochord: development of the hypochord in Xenopus.

The patterning and differentiation of the vertebrate endoderm requires signaling from adjacent tissues. In this report, we demonstrate that signals from the notochord are critical for the development of the hypochord, which is a transient, endodermally derived structure that lies immediately ventral to the notochord in the amphibian and fish embryo. It appears likely that the hypochord is required for the formation of the dorsal aorta in these organisms. We show that removal of the notochord during early neurulation leads to the complete failure of hypochord development and to the elimination of expression of the hypochord marker, VEGF. Removal of the notochord during late neurulation, however, does not interfere with hypochord formation. These results suggest that signals arising in the notochord instruct cells in the underlying endoderm to take on a hypochord fate during early neural stages, and that the hypochord does not depend on further notochord signals for maintenance. In reciprocal experiments, when the endoderm receives excess notochord signaling, a significantly enlarged hypochord develops. Overall, these results demonstrate that, in addition to patterning neural and mesodermal tissues, the notochord plays an important role in patterning of the endoderm.

Animals↗
PubMed2001

Xrel3 is required for head development in Xenopus laevis.

The Rel/NF-kappa B gene family encodes a large group of transcriptional activators involved in myriad differentiation events, including embryonic development. We have shown previously that Xrel3, a Xenopus Rel/NF-kappa B-related gene, is expressed in the forebrain, dorsal aspect of the mid- and hindbrain, the otocysts and notochord of neurula and larval stage embryos. Overexpression of Xrel3 causes formation of embryonic tumours. We now show that Xrel3-induced tumours and animal caps from embryos injected with Xrel3 RNA express Otx2, Shh and Gli1. Heterodimerisation of a C-terminally deleted mutant of Xrel3 with wild-type Xrel3 inhibits in vitro binding of wild-type Xrel3 to Rel/NF-kappa B consensus DNA sequences. This dominant interference mutant disrupts Shh, Gli1 and Otx2 mRNA patterning and inhibits anterior development when expressed in the dorsal side of zygotes, which is rescued by co-injecting wild-type Xrel3 mRNA. In chick development, Rel activates Shh signalling, which is required for normal limb formation; Shh, Gli1 and Otx2 encode important neural patterning elements in vertebrates. The activation of these genes in tumours by Xrel3 overexpression and the inhibition of their expression and head development by a dominant interference mutant of Xrel3 indicates that Rel/NF-kappa B is required for activation of these genes and for anterior neural patterning in Xenopus.

Animals↗
PubMed2001

BMP controls proximodistal outgrowth, via induction of the apical ectodermal ridge, and dorsoventral patterning in the vertebrate limb.

Dorsoventral (DV) patterning of the vertebrate limb requires the function of the transcription factor Engrailed 1 (EN1) in the ventral ectoderm. EN1 restricts, to the dorsal half of the limb, the expression of the two genes known to specify dorsal pattern. Limb growth along the proximodistal (PD) axis is controlled by the apical ectodermal ridge (AER), a specialized epithelium that forms at the distal junction between dorsal and ventral ectoderm. Using retroviral-mediated misexpression of the bone morphogenetic protein (BMP) antagonist Noggin or an activated form of the BMP receptor in the chick limb, we demonstrate that BMP plays a key role in both DV patterning and AER induction. Thus, the DV and PD axes are linked by a common signal. Loss and gain of BMP function experiments show that BMP signaling is both necessary and sufficient to regulate EN1 expression, and consequently DV patterning. Our results also indicate that BMPs are required during induction of the AER. Manipulation of BMP signaling results in either disruptions in the endogenous AER, leading to absent or severely truncated limbs or the formation of ectopic AERs that can direct outgrowth. Moreover, BMP controls the expression of the MSX transcription factors, and our results suggest that MSX acts downstream of BMP in AER induction. We propose that the BMP signal bifurcates at the level of EN1 and MSX to mediate differentially DV patterning and AER induction, respectively.

Animals↗
PubMed2004

Dorsoventral patterning of the mouse coat by Tbx15.

Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H)), affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t)) normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H) mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in de(H) that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in de(H)/de(H) animals. Construction of a targeted allele of Tbx15 confirmed that the de(H) phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie region-specific differences in body morphology.

Agouti Signaling Protein↗
PubMed2005

The rod photoreceptor pattern is set at the optic vesicle stage and requires spatially restricted cVax expression.

How and when positional identities in the neural retina are established have been addressed primarily with respect to the topographic projections of retinal ganglion cells onto their targets in the brain. Although retinotectal map formation is a prominent manifestation of retinal patterning, it is not the only one. Photoreceptor subtypes are arranged in distinct, species-specific patterns. The mechanisms used to establish photoreceptor patterns have been relatively unexplored at the mechanistic level. We performed ablations of the eye anlage in chickens and found that removal of the anterior or dorsal optic vesicle caused loss of the area centralis, which is a rod-free central area of the retina, and severely disorganized other aspects of the rod pattern. These observations indicate that the anteroposterior and dorsoventral distribution of rods is determined by the optic vesicle stage. To investigate the molecular mechanisms involved, the rod distribution was analyzed after viral misexpression of several patterning genes that were previously shown to be important in positional specification of retinal ganglion cells. Ectopic expression of FoxG1, SOHo1,or GH6 transcription factors expressed in the anterior optic vesicle and/or optic cup, respectively, did not affect the rod pattern. This pattern therefore appears to be specified by an activity acting before, or in parallel with, these factors. In contrast, misexpression of the ventrally restricted transcription factor, cVax, severely disturbed the rod pattern.

Animals↗
PubMed2000

SPC4/PACE4 regulates a TGFbeta signaling network during axis formation.

In vertebrates, specification of anteroposterior (A/P) and left-right (L/R) axes depends on TGFbeta-related signals, including Nodal, Lefty, and BMPs. Endoproteolytic maturation of these proteins is probably mediated by the proprotein convertase SPC1/Furin. In addition, precursor processing may be regulated by related activities such as SPC4 (also known as PACE4). Here, we show that a proportion of embryos lacking SPC4 develop situs ambiguus combined with left pulmonary isomerism or complex craniofacial malformations including cyclopia, or both. Gene expression analysis during early somite stages indicates that spc4 is genetically upstream of nodal, pitx2, lefty1, and lefty2 and perhaps maintains the balance between Nodal and BMP signaling in the lateral plate that is critical for L/R axis formation. Furthermore, genetic interactions between nodal and spc4, together with our analysis of chimeric embryos, strongly suggest that during A/P axis formation, SPC4 acts primarily in the foregut. These findings establish an important role for SPC4 in patterning the early mouse embryo.

Abnormalities, Multiple↗
PubMed1995

Body temperature and malaria parasitaemia in rural African children.

Body temperature was measured and the prevalence of malaria parasitaemia was determined in 198 rural school children aged 6-12 years in a hyperendemic area of southwest Nigeria over a 14 week period spanning part of both wet and dry seasons. Body temperature values in apparently healthy children and in children with malaria parasitaemia were similar with group mean of 37.1 to 37.3 degrees C and with little or no variation in these values with season. The proportion of individual measurements with values > 37.5 degrees C in the two groups were respectively 4.3 and 6%. Despite a seasonal variation in parasite rate, with the highest rates in the wet and the lowest rates in the dry season, there was no significant difference in the proportion of subjects with parasite density > 1000/ul between season. There was also no relationship between parasite density and body temperature. In general, children with parasitaemia < 1000/ul were not pyrexial and less than 2% of all episodes of detectable parasitaemia was accompanied by symptoms of acute malaria. These findings suggest that the presence of malaria parasitaemia has little or no effect on body temperature pattern in a group of rural school children in an endemic area.

Body Temperature↗
PubMed1993

Alcohol consumption, smoking habits and body fat distribution in Italian men and women aged 20-60 years.

The study was performed on 601 patients (294 males and 307 females) of a general practitioner. Alcohol intake and smoking habits were compared with other anthropometric measurements including waist-to-hip girth ratio. Patients were divided into non-smokers and smokers (subdivided into three groups according to the number of cigarettes smoked per day) and into non-drinkers and drinkers (subdivided into three groups with different alcohol intakes). Ex-smokers were excluded from the study. Analysis of covariance using age, body mass index, physical activity and menopausal status as covariates, showed that: (1) cigarette smoking is not accompanied by a specific pattern for body fat distribution; (2) waist-to-hip ratio was significantly different for the four classes of alcohol intake for women (non-drinkers: 0.809, < 11 g: 0.805, 11-20 g: 0.809, > 20 g: 0.826; F = 2.8, P < 0.05) but not for men (non-drinkers: 0.944, < 20 g: 0.934, 21-40 g: 0.940, > 40 g: 0.943; F = 0.9); (3) increased alcohol intake corresponds to an increased lipid and energy supply.

Adipose Tissue↗
PubMed1998

From pattern to gene, from gene to pattern.

Our understanding of animal development has been revolutionized by genetic approaches to the identification and isolation of pattern-regulating genes. In the past several years, fundamental embryological concepts such as morphogenetic fields, compartments, and organizers have been defined at a molecular level and visualized in developing animals. Here, I will discuss how the focus on the regulation and function of genes with dramatic effects on pattern formation, primarily by through the analysis of gene expression patterns as surrogates of physical pattern elements, has elucidated gene hierarchies that control developmental pathways.

Animals↗
PubMed1982

The relation between radiological patterns of the breast and body weight and height.

Mammograms were obtained from 942 normal volunteer women aged over 35 years, and were classified by Wolfe's criteria. There was no relationship between height and mammographic pattern. An increase in weight, whether corrected for height or not, was associated with an increase in the proportion of N grades and a concomitant decrease in DY grade mammograms. This effect reached formal significance in pre-menopausal women but was highly significant in post-menopausal women. For women who were either above or below their ideal weight there was a significant positive correlation between parity and the proportion of N and P1 mammograms. The slopes of the linear regression for these two groups were the same, although the elevation of the above-ideal weight group was significantly greater. This implies that for any given parity, there are about 16% more N or P1 grades in the above-ideal compared with the below-ideal weight group.

Adult↗
PubMed2001

Patterns of transfer of adaptation among body segments.

Two experiments were conducted in order to determine the patterns of transfer of visuomotor adaptation between arm and head pointing. An altered gain of display of pointing movements was used to induce a conflict between visual and somatosensory representations. Two subject groups participated in Experiment 1: group 1 adapted shoulder pointing movements, and group 2 adapted wrist pointing movements to a 0.5 gain of display. Following the adaptation regimen, subjects performed a transfer test in which the shoulder group performed wrist movements and the wrist group performed shoulder movements. The results demonstrated that both groups displayed typical adaptation curves, initially undershooting the target followed by a return to baseline performance. Transfer tests revealed that both groups had high transfer of the acquired adaptation to the other joint. Experiment 2 followed a similar design except that group 1 adapted head pointing movements and group 2 adapted arm pointing movements. The arm adaptation had high transfer to head pointing while the head adaptation had very little transfer to arm pointing. These results imply that, while the arm segments may share a common target representation for goal-directed actions, individual but functionally dependent target representations may exist for the control of head and arm movements.

Adaptation, Physiological↗
PubMed1999

A Wnt signaling system that specifies two patterns of cell migration in C. elegans.

In C. elegans, a bilateral pair of neuroblasts, QL and QR, give rise to cells that migrate in opposite directions along the anteroposterior (A/P) body axis. QL and its descendants migrate posteriorly whereas QR and its descendants migrate anteriorly. We find that a Wnt family member, EGL-20, acts in a dose-dependent manner to specify these opposite migratory behaviors. High levels of EGL-20 promote posterior migration by activating a canonical Wnt signal transduction pathway, whereas low levels promote anterior migration by activating a separate, undefined pathway. We find that the two Q cells respond differently to EGL-20 because they have different response thresholds. Thus, in this system two distinct dose-dependent responses are specified not by graded levels of the Wnt signal, but instead by left-right asymmetrical differences in the cellular responsiveness to Wnt signaling.

Animals↗