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PubMed2003

Vascular development and patterning: making the right choices.

The developing vascular system is regulated by a series of intrinsic and extrinsic signaling interactions that result in the formation and specialization of vessels that circulate blood and lymph around the body. Signaling molecules, such as vascular epithelial growth factors (VEGFs) and angiopoietins, that establish the cellular identity of the endothelial cells in the early embryo also play roles in establishing whether developing vessels will be arterial, venous or lymphatic. Genetic studies in zebrafish and mice have suggested a key role for Notch signaling, downstream of VEGF-A, in specifying arterial versus venous fate, and for VEGF-C and -D, along with the transcription factor, Prox1, in specifying lymphatic fate.

Angiopoietins↗
PubMed1983

Body weight changes throughout pregnancy in the common marmoset Callithrix jacchus.

Adult female common marmosets were weighed weekly for periods of 6-30 months. Of 27 animals, 25 were pregnant at some stage of the investigation. Patterns of body weight change throughout singleton, twin and triplet pregnancies were obtained and compared. Maternal weight increase was dependent on the number of young in utero; however, little or no change in weight was observed during the first 13 weeks of gestation, irrespective of the number of offspring delivered subsequently. The overall maternal:fetal body weight ratio was 1.00:0.21, ranging from 1.00:0.11 for singleton to 1.00:0.26 for triplet pregnancies. Lactation had little or no effect on maternal body weight during the first 4 weeks postpartum.

Animals↗
PubMed1993

Age differences in movement patterns used to rise from a bed in subjects in the third through fifth decades of age.

BACKGROUND AND PURPOSE: The purposes of this study were to describe the movement patterns of middle-aged adults when rising from a bed and to determine whether there are age-related differences in movement patterns across the third through fifth decades of age. SUBJECTS: Ninety-three adults (30 men, 63 women), ranging in age from 30 to 59 years, participated in the study. METHODS: The subjects were videotaped during 10 trials of rising from a bed. Subjects comprised three age groups, as defined by the decades of the thirties, forties, and fifties. Movement patterns for four body regions were used to classify the videotaped performances. The incidence of each movement pattern was determined for each decade and graphed. RESULTS: Subjects in their thirties differed from older subjects in movement patterns used to rise from a bed. Movement pattern incidence varied across age groups for each body region. The movement patterns of one body region predominated in reverse order of a previously proposed developmental sequence. CONCLUSION AND DISCUSSION: Results indicate physical therapists should consider the patient's age when selecting movement patterns to teach.

Activities of Daily Living↗
PubMedDate not supplied

Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease.

Differences in body fat distribution between diabetics and nondiabetics have been recognized for several decades; diabetics have a more centralized or upper body fat pattern than nondiabetics. Recently, attention has focused on fat patterning and also on hyperinsulinemia as possible risk factors for cardiovascular disease, as well. The case for insulin as a cardiovascular risk factor is bolstered by theoretical considerations related to its possibly atherogenic effects on serum and arterial wall lipids. Empirical evidence for fat patterning and hyperinsulinemia as cardiovascular risk factors rests on six prospective epidemiologic studies, three on fat patterning and three on insulin. Although provocative, none of these studies can be regarded as definitive. In none was a dose-response effect demonstrated, and there are various inconsistencies within and across the studies. Moreover, in none of the studies were hyperinsulinemia and fat patterning evaluated simultaneously. This is of particular importance in view of the well-documented interrelationships between these two variables. For example, insulin resistance and hyperinsulinemia have been found to be greater in women with upper body obesity compared to women with lower body obesity of equivalent degree. Considerable progress has been made recently in understanding the mechanisms of the differential metabolic effects of these two types of obesity. The extent to which fat patterning and hyperinsulinemia are genetic or acquired has received relatively little attention. Further research on this question is warranted since elucidation of any environmental influences on these variables might suggest new clinical and public health control measures.

Adipose Tissue↗
PubMed2005

Scaling the daily oscillations of breathing frequency and skin temperature in mammals.

Among mammals, the peak-trough difference (PTD) of the circadian pattern of body temperature (T(b)) drops very little with the increase in body mass (W), despite the large increase in heat capacitance and thermal inertia. We asked whether this might be contributed by systematic differences in the circadian pattern of breathing frequency (f) and skin temperature (Tskin), which are parts of the control mechanisms of heat loss. Measurements had been conducted on animals of eight species, chosen to cover a four-fold range in W, while resting and awake. The oscillation of f preceded that of T(b) in 7 of the 8 species, and its acrophase did not correlate with W. The daily mean and PTD of f scaled with W in a similar manner (respectively, W(-)(23) and W(-)(0.29)), the PTD averaging about 20% of the daily mean. The circadian oscillations of Tskin, measured in specimens of five species at three locations (abdomen, ear and thigh), were in phase with T(b). Neither the PTD nor the acrophase of Tskin changed systematically with W. The differences between T(b) and Tskin (means, peaks and troughs) decreased significantly with W; on average, the T(b)-Tskin difference scaled to W(-)(0.19). In conclusion, the relative amplitudes and the acrophase of Tskin and f did not show systematic inter-species differences. The progressive increase of Tskin with W could be a factor in maintaining the PTD of T(b) within a narrow range among mammals of very different size.

Animals↗
PubMed1998

Clocked gene expression in somite formation.

A recent paper describes a striking expression pattern during somite formation for a chick ortholog of the fly hairy gene. Before segmentation, c-hairy1 mRNA oscillates in the presomitic mesoderm such that three distinct spatial patterns are seen. The authors use a series of ingenious manipulations to show that these phases follow each other in time, adding up to a 90-minute periodicity in c-hairy1 expression. The discovery of this clock of gene expression emphasizes the importance of temporally regulated events in the establishment of spatial patterns.

Animals↗
PubMed2004

Neuroblast formation and patterning during early brain development in Drosophila.

The Drosophila embryo provides a useful model system to study the mechanisms that lead to pattern and cell diversity in the central nervous system (CNS). The Drosophila CNS, which encompasses the brain and the ventral nerve cord, develops from a bilaterally symmetrical neuroectoderm, which gives rise to neural stem cells, called neuroblasts. The structure of the embryonic ventral nerve cord is relatively simple, consisting of a sequence of repeated segmental units (neuromeres), and the mechanisms controlling the formation and specification of the neuroblasts that form these neuromeres are quite well understood. Owing to the much higher complexity and hidden segmental organization of the brain, our understanding of its development is still rudimentary. Recent investigations on the expression and function of proneural genes, segmentation genes, dorsoventral-patterning genes and a number of other genes have provided new insight into the principles of neuroblast formation and patterning during embryonic development of the fly brain. Comparisons with the same processes in the trunk help us to understand what makes the brain different from the ventral nerve cord. Several parallels in early brain patterning between the fly and the vertebrate systems have become evident.

Animals↗
PubMed1999

Three different noggin genes antagonize the activity of bone morphogenetic proteins in the zebrafish embryo.

The dorsoventral polarity of the vertebrate embryo is established through interactions between ventrally expressed bone morphogenetic proteins and their organizer-borne antagonists Noggin, Chordin, and Follistatin. While the opposing interactions between Short Gastrulation/Chordin and Decapentaplegic/BMP4 have been evolutionarily conserved in arthropods and vertebrates, there has been up to now no functional evidence of an implication of Noggin in the early patterning of organisms other than Xenopus. We have studied the contribution of Noggin to the embryonic development of the zebrafish. While single-copy noggin genes have been characterized in several vertebrate species, we report that the zebrafish genome harbors three noggin homologues. Overexpression experiments show that Noggin1, Noggin2, and Noggin3 can antagonize ventralizing BMPs. While all three factors have similar biological activities, their embryonic expression is different. The combined expression of the three genes recapitulates the different aspects of the expression of the single-copy noggin genes of other organisms. This suggests that the three zebrafish noggin genes and the single noggin genes of other vertebrates have evolved from a common ancestor and that subsequent differential loss of tissue-specific elements in the promoters of the different zebrafish genes accounts for their more restricted spatiotemporal expression. Finally we show that noggin1 is expressed in the fish organizer and able to dorsalize the embryo, suggesting its implication in the dorsoventral patterning of the zebrafish.

Amino Acid Sequence↗
PubMed2001

Specification and morphogenesis of the zebrafish larval head skeleton.

Forward genetic analyses can reveal important developmental regulatory genes and how they function to pattern morphology. This is because a mutated gene can produce a novel, sometimes beautiful, phenotype that, like the normal phenotype, immediately seems worth understanding. Generally the loss-of-function mutant phenotype is simplified from the wild-type one, and often the nature of the pattern simplification allows one to deduce how the wild-type gene contributes to patterning the normal, more complex, morphology. This truism seems no less valid for the vertebrate head skeleton than for other and simpler cases of patterning in multicellular plants and animals. To show this, we review selected zebrafish craniofacial mutants. "Midline group" mutations, in genes functioning in one of at least three signal transduction pathways, lead to neurocranial pattern truncations that are primarily along the mediolateral axis. Mutation of lazarus/pbx4, encoding a hox gene partner, and mutation of valentino/kreisler, a hox gene regulator, produce anterior-posterior axis disruptions of pharyngeal cartilages. Dorsoventral axis patterning of the same cartilages is disrupted in sucker/endothelin-1 mutants. We infer that different signal transduction pathways pattern cartilage development along these three separate axes. Patterning of at least the anterior-posterior and dorsoventral axes have been broadly conserved, e.g., reduced Endothelin-1 signaling similarly perturbs cartilage specification in chick, mouse, and zebrafish. We hypothesize that Endothelin-1 also is an upstream organizer of the patterns of cellular interactions during cartilage morphogenesis.

Animals↗
PubMed2005

Does the isthmic organizer influence D/V patterning of the midbrain?

Early brain and spinal cord regionalization along the dorsoventral axis are thought to be governed by similar mechanisms. Subsequently, the size of the alar plate of the neural tube increases dramatically in the midbrain and anterior forebrain, compared to the spinal cord. This suggests that additional mechanisms may be required to refine A/P and D/V patterning in these structures. The isthmic organizer is a signaling center that controls both growth and patterning in the midbrain and anterior hindbrain through the production of several secreted molecules, in particular FGF8. Several studies have indicated that the isthmic organizer is involved in the positioning and development of the midbrain roof and floor plates, the two structures that respectively mark the dorsal and ventral axis of the neural tube. It remains unclear whether its influence on axis formation in the midbrain is a consequence of a more general function of the isthmic organizer/FGF8 as a modulator of DV patterning or if selection of an axis is a necessary and general by-product of its organizing function not directly related to D/V patterning. In this paper, we review the current data supporting each possibility.

Animals↗
PubMed2006

Area and layer patterning in the developing cerebral cortex.

Two anatomical patterns characterize the neocortex, and both are essential for normal cortical function. First, neocortex is divided into anatomically distinct and functionally specialized areas that form a species-specific map. Second, neocortex is composed of layers that organize cortical connectivity. Recent studies of layer and area development have used time-lapse microscopy to follow cortical cell division and migration, gene arrays to find layer- or area- specific regulatory genes, time- and region- specific manipulations of candidate genes, and optical imaging to compare area maps in wild type with genetically altered mice. New observations clarify the molecular and cellular mechanisms that generate each pattern, and stress the links between layer and area formation.

Animals↗
PubMed2004

Extracellular matrix dynamics during vertebrate axis formation.

The first evidence for the dynamics of in vivo extracellular matrix (ECM) pattern formation during embryogenesis is presented below. Fibrillin 2 filaments were tracked for 12 h throughout the avian intraembryonic mesoderm using automated light microscopy and algorithms of our design. The data show that these ECM filaments have a reproducible morphogenic destiny that is characterized by directed transport. Fibrillin 2 particles initially deposited in the segmental plate mesoderm are translocated along an unexpected trajectory where they eventually polymerize into an intricate scaffold of cables parallel to the anterior-posterior axis. The cables coalesce near the midline before the appearance of the next-formed somite. Moreover, the ECM filaments define global tissue movements with high precision because the filaments act as passive motion tracers. Quantification of individual and collective filament "behaviors" establish fate maps, trajectories, and velocities. These data reveal a caudally propagating traveling wave pattern in the morphogenetic movements of early axis formation. We conjecture that within vertebrate embryos, long-range mechanical tension fields are coupled to both large-scale patterning and local organization of the ECM. Thus, physical forces or stress fields are essential requirements for executing an emergent developmental pattern-in this case, paraxial fibrillin cable assembly.

Animals↗
PubMed2003

Yin Yang 1, a vertebrate polycomb group gene, regulates antero-posterior neural patterning.

Polycomb group (PcG) genes are required for the stable repression of the homeotic genes and other developmentally regulated genes. Yin Yang 1 (YY1), a vertebrate homolog of the Drosophila PcG pleiohomeotic (Pho), is a multifunctional protein that can act as a repressor or activator of transcription. Xenopus YY1 (XYY1) protein was localized in the central nervous system (CNS), particularly anterior neural tube of tailbud stage embryos. To elucidate the role of endogenous XYY1, loss-of-function studies were performed using XYY1 antisense morpholino oligonucleotide (XYY1 MO). Inhibition of XYY1 function resulted in embryos with antero-posterior axial patterning defects and reduction of head structures. XYY1 MO also reduced the expression of En2, a midbrain/hindbrain junction marker, which was rescued by co-injection of XYY1 mRNA. However, XYY1 MO-injection did not affect the expression of HoxB9, a spinal cord marker. These results suggest that YY1 controls antero-posterior patterning of the CNS during Xenopus embryonic development.

Animals↗
PubMed1998

Zebrafish wnt11: pattern and regulation of the expression by the yolk cell and No tail activity.

This study analyzed the spatial and temporal expression pattern of zebrafish wnt11 and the regulation of the expression during zebrafish early development, focusing on the interaction with the no tail (ntl) gene, a zebrafish orthologue of mouse Brachyury (T). Zygotic expression of wnt11 was first detected at the late blastula stage in the blastoderm margin, a presumptive mesoderm region. wnt11 expression coincided with mesoderm induction, and the expression was induced by mesoderm inducers such as the yolk cell (Mizuno, T., Yamaha, E., Wakahara, M., Kuroiwa, A., Takeda, H., 1996. Mesoderm induction in zebrafish. Nature 383, 131-132) or FGFs, indicating that, like ntl, wnt11 is one of the immediate-early genes in mesoderm induction. Initial expression domains of wnt11 and ntl overlapped, and these genes showed a similar response to mesoderm inducers. However, analysis of the ntl mutant embryos suggested that wnt11 and ntl are placed in distinct genetic pathways; the ntl mutation had no effect on wnt11 expression in the blastoderm margin. This was further supported by the result of RNA injection experiments showing that overexpression of Wnt11 did not affect ntl expression in the margin. Thus, wnt11 and ntl expression are induced and maintained independently in their initial phase of expression. In later stages, wnt11 was expressed in various organs, such as the somites, particularly in the developing notochord. Since no wnt gene has been reported to be expressed in the axial mesoderm, which is known to act as a signaling source that patterns the neural tube and somites, zebrafish wnt11 is the first wnt gene expressed in the notochord. Furthermore, in contrast to early expression, wnt11 expression in the notochord depended on Ntl activity. In the ntl mutant in which somite patterning is severely affected, wnt11 expression was completely lost, while another signaling molecule, sonic hedgehog is expressed in the mutant notochord precursor cells (Krauss, S., Concordet, J.-P., Ingham, P.W., 1993. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75, 1431-1444). wnt11 expression in the somite also shows a characteristic pattern, correlated with the migration and differentiation of slow muscle precursors. These observations suggest a role for wnt11 in patterning the somites.

Amino Acid Sequence↗
PubMed1998

lunatic fringe is an essential mediator of somite segmentation and patterning.

The gene lunatic fringe encodes a secreted factor with significant sequence similarity to the Drosophila gene fringe. fringe has been proposed to function as a boundary-specific signalling molecule in the wing imaginal disc, where it is required to localize signalling activity by the protein Notch to the presumptive wing margin. By targeted disruption in mouse embryos, we show here that lunatic fringe is likewise required for boundary formation. lunatic fringe mutants fail to form boundaries between individual somites, the initial segmental unit of the vertebrate trunk. In addition, the normal alternating rostral-caudal pattern of the somitic mesoderm is disrupted, suggesting that intersomitic boundary formation and rostral-caudal patterning of somites are mechanistically linked by a process that requires lunatic fringe activity. As a result, the derivatives of the somitic mesoderm, especially the axial skeleton, are severely disorganized in lunatic fringe mutants. Taken together, our results demonstrate an essential function for a vertebrate fringe homologue and suggest a model in which lunatic fringe modulates Notch signalling in the segmental plate to regulate somitogenesis and rostral-caudal patterning of somites simultaneously.

Animals↗