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PubMedDate not supplied

Is local metabolism the basis of the fractal vascular structure in the heart?

The distribution of blood flow in the heart muscle is very heterogeneous and shows a self-similar fractal pattern, extending to small spatial scales. It is very likely that local oxygen consumption is more or less proportional to local blood flow and that local aerobic metabolism also is very heterogeneous. It is not yet clear whether local metabolism is heterogeneous in origin and the distribution of flow has secondarily adapted to metabolism, or, the other way around, whether flow is primarily heterogeneous because of the irregular structure of the coronary tree and flow has adapted to metabolism. Little is known yet about the developmental and adaptive mechanisms which bring about mutual adjustment between vascular growth and local metabolic demand, and genes and growth factors involved in shaping the structure of the coronary tree have only begun to be identified. Fractal and nonlinear dynamic mathematical models generate complex heterogeneous structures from simple nonlinear deterministic rules which are recursively applied. Such nonlinear models may thus help to explain the generation of large vascular trees regulated by synergy of a limited number of genes and signaling molecules. This may explain the relative regularity of space filling of the vascular tree and the asymmetry of branching and flow distribution in the tree.

Animals↗
PubMed2005

Functional redundancy of PIN proteins is accompanied by auxin-dependent cross-regulation of PIN expression.

Plant development displays an exceptional plasticity and adaptability that involves the dynamic, asymmetric distribution of the phytohormone auxin. Polar auxin flow, which requires polarly localized transport facilitators of the PIN family, largely contributes to the establishment and maintenance of the auxin gradients. Functionally overlapping action of PIN proteins mediates multiple developmental processes, including embryo formation, organ development and tropisms. Here we show that PIN proteins exhibit synergistic interactions, which involve cross-regulation of PIN gene expression in pin mutants or plants with inhibited auxin transport. Auxin itself positively feeds back on PIN gene expression in a tissue-specific manner through an AUX/IAA-dependent signalling pathway. This regulatory switch is indicative of a mechanism by which the loss of a specific PIN protein is compensated for by auxin-dependent ectopic expression of its homologues. The compensatory properties of the PIN-dependent transport network might enable the stabilization of auxin gradients and potentially contribute to the robustness of plant adaptive development.

Arabidopsis↗
PubMed1995

arc6, an extreme chloroplast division mutant of Arabidopsis also alters proplastid proliferation and morphology in shoot and root apices.

The arc6 (accumulation and replication of chloroplasts) mutant of Arabidopsis has only two greatly enlarged chloroplasts per mature leaf mesophyll cell compared with ninety chloroplasts per cell in the wild type. The mutation is a single nuclear gene and the plant phenotype is normal. Shoot and root apical meristems of arc6 plants have been examined to determine how early during plastid development the mutant arc6 phenotype can be recognised. In the cells of the arc6 apical meristem there are only two proplastids, which are larger than wild type with a highly variable morphology. In the cells of the leaf primordia where differentiation of proplastids to chloroplasts occurs arc6 plastids are larger and at a more advanced developmental stage than wild-type plastids. In arc6 root cells statoliths and other plastids also show grossly abnormal morphology and the statoliths are greatly increased in size. During arc6 stomatal guard cell development the perturbation in proplastid population dynamics affects plastid segregation and 30% of stomata lack plastids in one or both guard cells. Our evidence would suggest that ARC6 is expressed throughout the vegetative cells of the Arabidopsis seedling with major effects on both the proplastid phenotype and the proplastid population. ARC6 is the first gene to be identified in Arabidopsis which has a global effect on plastid development in cells arising from both the shoot and root meristems, and is of major importance in the nuclear control of plastid differentiation in higher plants.

Arabidopsis↗
PubMed2001

[Endogenous and exogenous evoked potentials in the most common neurologic syndromes during development].

This paper presents the application of endo- and egzogenic evoked potentials (EP) in the most frequent neurological syndromes in children and adolescents on the basis of the author's own experiences. The advantages of the method are: objectiveness, noninvasive and the possibility of numerous repetitions. The principles of EPs application and interpretation are established by the recommendations of the International Federation of Clinical Neurophysiology. The analysis of the results contains morphology of recording, latencies and amplitudes of potentials. EPs constitute the important research method in child neurology. They are useful in diagnostics of demyelinating, degenerative and metabolic diseases, tumours of the nervous system, phacomatoses, infections and cerebrovascular disorders, CNS traumas and in cases of psychomotor retardation. The importance of this method consists in 1. diagnosis of symptomatic and asymptomatic pathological processes, 2. localization of the lesion, 3. confirmation of clinical diagnosis, 4. aid in differentiation, 5. monitoring of the treatment, 6. observation of the disease dynamics, 7. evaluation of the prognosis. Endogenic potentials enable neurophysiological evaluation of cognitive processes. Especially P 300 is analyzed in the range of its latency, amplitude and topography. P 300 is evaluated in relation to syndromes and diseases of developmental age, mostly in epilepsy, headaches, tumours, CVS traumas and minimal brain dysfunction.

Adolescent↗
PubMedDate not supplied

[Uptake of Testosterone-1 alpha, 2 alpha-3H(n) by target organ tissues of guinea pig embryos in vitro].

The dynamics of testosterone-1 alpha, 2 alpha-3H(n) intake by different tissues of genital tract was studied in the guinea pig embryos from the 23rd day of development till birth. The specific intake was noted at all developmental stages studied and in all genital tract rudiments. The Selective intake was observed in the male embryos in the genital tubercle from the 29th day, in the ducts from the 46th day and in the urogenital sinus from the 26th day. In the female embryos it was found in the genital tubercle on the 26--28th day and from the 35th, in the ducts from the 46th day and in the urogenital sinus on the 32--35th, 46--50th days and prior to birth. The specific intake was also observed in the gonads of embryos of both sexes. The data obtained suggest the presence of reception to androgen prior to the beginning of morphogenesis of the genital system and the acquisition of increase sensitivity to the hormone in the homologous rudiments during the critical periods of differentiation of organ targets by the male type.

Animals↗
PubMed2002

Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches.

The Drosophila segment polarity genes constitute the last tier in the segmentation cascade; their job is to maintain the boundaries between parasegments and provide positional "read-outs" within each parasegment for the entire developmental history of the animal. These genes constitute a relatively well-defined network with a relatively well-understood patterning task. In a previous publication (von Dassow et al. 2000. Nature 406:188-192) we showed that a computer model predicts the segment polarity network to be a robust boundary-making device. Here we elaborate those findings. First, we explore the constraints among parameters that govern the network model. Second, we test architectural variants of the core network, and show that the network tolerates a wide variety of adjustments in design. Third, we evaluate several topologically identical models that incorporate more or less molecular detail, finding that more-complex models perform noticeably better than simplified ones. Fourth, we discuss two instances in which the failure of the network model to behave in a life-like fashion highlights mechanistic details that need further experimental investigation. We conclude with an explanation of how the segment polarity network can be understood as an interwoven conspiracy of simple dynamical elements, several bistable switches and a homeostat. The robustness with which the network as a whole maintains a spatial regime of stable cell state emerges from generic dynamical properties of these simple elements.

Animals↗
PubMed2005

Developmental expression of the high mobility group B gene in the amphioxus, Branchiostoma belcheri tsingtauense.

High-Mobility Group (HMG) B proteins are abundant and highly conserved non-histone proteins, which play an important architectural role in the assembly of nucleoprotein complexes and in the Regulation of transcription. These proteins have also been shown to play key roles during embryonic development and cell differentiation. Here we report a full-length cDNA sequence of the HMG protein, AmphiHMGB from Amphioxus. Sequence analysis indicates that this putative AmphiHMGB protein contains four domains: HMG-box A, HMG-box B, basic region, acidic carboxyl-terminal tail and a linker. Phylogenetic analysis suggests that AmphiHMGB falls outside the vertebrate clade. HMGB gene duplication occurred near the base of the vertebrate gene Clade. The dynamic expression of AmphiHMGB during embryonic development reveals for the first time that it may involve differentiation of neural ectoderm, mesoderm and endoderm in this animal.

Amino Acid Sequence↗
PubMed1994

Dynamic expression patterns of tenascin, proteoglycans, and cell adhesion molecules during human hair follicle morphogenesis.

The development of skin appendages such as hair, feathers, and teeth is brought about by reciprocal interactions between epidermal and mesenchymal tissues and is thought to be influenced in part by cell adhesion molecules and components of the extracellular matrix. The developmental distributions of tenascin, neural cell adhesion molecule (NCAM), E-cadherin, intercellular adhesion molecule 1 (ICAM-1), chondroitin sulfate proteoglycan (CSPG), and the heparan sulfate proteoglycan perlecan were studied in relation to hair follicle morphogenesis in fetal human skin. Tenascin first appeared in developing skin in focal concentrations at the epidermal-mesenchymal interface, just prior to, and presumably correlated with, hair follicle initiation. Tenascin immunostaining remained prominent in the basement membrane zone and extracellular matrix of the follicle sheath during subsequent morphogenetic stages. Two forms of tenascin (M(r) 250 x 10(3) and 280-300 x 10(3)), were revealed by Western blots of skin extracts. NCAM immunolabeling was initially present throughout the dermis, and became progressively restricted to the dermal condensation and the follicle sheath. Western blot analysis revealed an isoform of NCAM (M(r) 160 x 10(3)) which lacked polysialic acid. At all stages, E-cadherin staining was diminished on follicle cells situated adjacent to the basement membrane, relative to cells in the follicle interior. Follicle-specific immunostaining for ICAM-1 was transient, appearing only at the pre-germ and hair germ stages of development. Antibodies to three distinct CSPG determinants revealed unique immunolabeling patterns following follicle initiation: One CSPG epitope co-distributed with tenascin in the follicle basement membrane and follicle sheath extracellular matrix; one CSPG epitope was similarly expressed, and was also found on follicle epithelial cells; and the third CSPG determinant was noticeably absent from the follicle sheath during elongation of the developing appendage. Perlecan was concentrated in the dermal papilla, in addition to its distribution in all skin basement membranes. A model for how these diverse molecules may interact to influence human hair follicle morphogenesis is presented.

Blotting, Western↗
PubMed2005

Patterns of continuity: a dynamic model for conceptualizing the stability of individual differences in psychological constructs across the life course.

In contemporary psychology there is debate over whether individual differences in psychological constructs are stable over extended periods of time. The authors argue that it is impossible to resolve such debates unless researchers focus on patterns of stability and the developmental mechanisms that may give rise to them. To facilitate this shift in emphasis, they describe a formal model that integrates 3 developmental processes: stochastic-contextual processes, person-environment transactions, and developmental constancies. The theoretical and mathematical analyses indicate that this model makes novel predictions about the way in which test-retest correlations are structured across a wide range of ages and test-retest intervals. The authors illustrate the utility of the model by comparing its predictions against meta-analytic data on Neuroticism. The discussion emphasizes the value of focusing on patterns of continuity, not only as phenomena to be explained but as data capable of clarifying the developmental processes underlying stability and change for a variety of psychological constructs.

Humans↗
PubMed2006

Differential regulation of Tbx5 protein expression and sub-cellular localization during heart development.

The T-box transcription factor Tbx5 can interact with Nkx2.5 and Gata4 transcription factors to synergistically regulate heart-specific genes in the nucleus. While a nuclear role for Tbx5 is clearly defined, we have previously shown that Tbx5 shuttles from nuclear to cytoplasmic sites, forming a complex with the PDZ-LIM protein LMP4 on the actin cytoskeleton. In this study, using a developmental series of chicken hearts, we provide the first evidence for differential Tbx5 protein expression and sub-cellular localization during cardiogenesis. At the tissue level, we show temporally and spatially restricted Tbx5 co-expression with LMP4. In cells co-expressing LMP4 and Tbx5 we demonstrate dynamic Tbx5 re-localization from exclusively nuclear to nuclear and cytoplasmic expression in the atrio-ventricular cushion. Furthermore, in coronary vessel development we show exclusive cytoplasmic localization of Tbx5, indicating a function for Tbx5 in the cytoplasm. In addition, we discover unknown regulation of Tbx5 and LMP4 expression in epicardial tissue, suggesting a specific role for Tbx5 in epicardial formation. These studies provide in vivo significance of the LMP4/Tbx5 protein interaction, suggesting both nuclear and cytoplasmic roles for Tbx5. The shuttling between nuclear and cytoplasmic sites reveals a novel mechanism for Tbx transcription factor regulation in chicken heart development allowing new insights for a better understanding of the molecular basis of hand/heart birth defects associated with TBX5 mutations.

Active Transport, Cell Nucleus↗
PubMed2005

Origination and innovation in the vertebrate limb skeleton: an epigenetic perspective.

The vertebrate limb has provided evolutionary and developmental biologists with grist for theory and experiment for at least a century. Its most salient features are its pattern of discrete skeletal elements, the general proximodistal increase in element number as development proceeds, and the individualization of size and shape of the elements in line with functional requirements. Despite increased knowledge of molecular changes during limb development, however, the mechanisms for origination and innovation of the vertebrate limb pattern are still uncertain. We suggest that the bauplan of the limb is based on an interplay of genetic and epigenetic processes; in particular, the self-organizing properties of precartilage mesenchymal tissue are proposed to provide the basis for its ability to generate regularly spaced nodules and rods of cartilage. We provide an experimentally based "core" set of cellular and molecular processes in limb mesenchyme that, under realistic conditions, exhibit the requisite self-organizing behavior for pattern origination. We describe simulations that show that under limb bud-like geometries the core mechanism gives rise to skeletons with authentic proximodistal spatiotemporal organization. Finally, we propose that evolution refines skeletal templates generated by this process by mobilizing accessory molecular and biomechanical regulatory processes to shape the developing limb and its individual elements. Morphological innovation may take place when such modulatory processes exceed a threshold defined by the dynamics of the skeletogenic system and elements are added or lost.

Animals↗
PubMed2003

Developmental regulation of hyaluronan-binding protein (RHAMM/IHABP) expression in early bovine embryos.

Hyaluronan or hyaluronic acid (HA) is a normal component of mammalian follicular, oviduct, and uterine fluids. Granulosa and expanding cumulus cells secrete large amounts of HA, and when HA is added in maturation and culture media, it improves the developmental potential of oocytes and embryos. HA regulates gene expression, signaling, proliferation, motility, adhesion, and morphogenesis. Many of these biological activities of HA are mediated through binding to the receptor for HA-mediated motility/intracellular HA-binding protein (RHAMM/IHABP). We evaluated the presence and dynamics of RHAMM/IHABP mRNA and protein expression in different stages of in vitro-produced bovine embryos using quantitative reverse transcriptase-real time-polymerase chain reaction and immunohistochemistry. We also analyzed the effects of different culture systems on the relative abundance of RHAMM/IHABP transcripts. RHAMM/IHABP mRNA levels decreased from the 2-cell to the 16-cell stage, increased again at the morula stage, and reached their highest level at the expanded blastocyst stage. RHAMM/IHABP mRNA abundance was significantly (P < 0.05) lower in embryos recovered in serum-containing medium than in embryos from serum-free media. Immunohistochemistry revealed the presence of RHAMM/IHABP first in 8-cell stages. Whereas RHAMM staining in 8-cell and morula stages was intense, it was weaker in blastocysts. Embryonic secretion of HA increased from the 2-cell stage until the 8-cell stage and then decreased in 16-cell embryos. After this, HA secretion increased in expanded and hatched blastocyst stages. These data suggest that the positive effects of HA on in vitro-produced bovine embryos may be mediated at least in part by RHAMM/IHABP.

Animals↗
PubMed2002

Developmental expression of EphA4-tyrosine kinase receptor in the mouse brain and spinal cord.

Eph receptor tyrosine kinases and their ephrin ligands are involved in some of the most important steps during the development of the central nervous system, including cell migration, axon guidance, topographic mapping and synapse formation. Moreover, in the adult, they have been implicated in plasticity and regulation of neural stem cell function. One member of the Eph family, EphA4, can bind to both classes of ephrins and may have multiple functions in nervous system development. In order to look for potential sites of EphA4 action during central nervous system development, we conducted a spatio-temporal analysis of EphA4 protein expression. We used immunohistochemistry in preference to in situ hybridization because of the high likelihood that EphA4 protein is expressed on axon tracts, long distances from EphA4 mRNA. In the telencephalon, EphA4 was expressed in the developing cortex from embryonic day 11 (E11) and, later, on major cortical tracts including the corpus callosum and cortico-spinal tract. Robust EphA4 expression was also found in the hippocampus and fornix, and cells and tracts in the striatum. In the diencephalon, the thalamus, the hypothalamus and thalamo-cortical projection were strongly positive. In the mesencephalon, a number of different nuclei were weakly positive, most prominently the red nucleus. In the rhombencephalon, many nuclei were strongly positive including the cerebellum and one of its afferent paths, the inferior cerebellar peduncle, as well as the olivary region. In the spinal cord, there was a dynamic pattern of expression through development, with persistent expression in the dorsal funiculus and ventral grey matter.

Animals↗
PubMed2002

Developmental expression of EphA4-tyrosine kinase receptor in the mouse brain and spinal cord.

Eph receptor tyrosine kinases and their ephrin ligands are involved in some of the most important steps during the development of the central nervous system, including cell migration, axon guidance, topographic mapping and synapse formation. Moreover, in the adult, they have been implicated in plasticity and regulation of neural stem cell function. One member of the Eph family, EphA4, can bind to both classes of ephrins and may have multiple functions in nervous system development. In order to look for potential sites of EphA4 action during central nervous system development, we conducted a spatio-temporal analysis of EphA4 protein expression. We used immunohistochemistry in preference to in situ hybridization because of the high likelihood that EphA4 protein is expressed on axon tracts, long distances from EphA4 mRNA. In the telencephalon, EphA4 was expressed in the developing cortex from embryonic day 11 (E11) and, later, on major cortical tracts including the corpus callosum and cortico-spinal tract. Robust EphA4 expression was also found in the hippocampus and fornix, and cells and tracts in the striatum. In the diencephalon, the thalamus, the hypothalamus and thalamo-cortical projection were strongly positive. In the mesencephalon, a number of different nuclei were weakly positive, most prominently the red nucleus. In the rhombencephalon, many nuclei were strongly positive including the cerebellum and one of its afferent paths, the inferior cerebellar peduncle, as well as the olivary region. In the spinal cord, there was a dynamic pattern of expression through development, with persistent expression in the dorsal funiculus and ventral grey matter.

Animals↗
PubMed2004

Analysis of cCx39 expression pattern during chick development.

The present study reports the expression pattern of connexin39 (cCx39) in chick embryos at different stages of central nervous system development. We examined the expression between HH17 and HH40 developmental stages of chicken embryos by in situ hybridization (ISH) technique. Connexin39 was first expressed at HH17. It stained neuroepithelial cells in the optic (OV) and telencephalic (TEL) vesicles, plus in the superficial mesenchyme of the two rostral branchial arches (maxilar and mandibular). These cells probably originated from the neural crest. This expression pattern changed drastically between stages HH17 and HH23, while it showed relatively little modifications from HH23 to HH29. At these times, connexin39 was expressed in three regions: the telencephalic vesicle, the diencephalon and the isthmus. At later stages, HH35 and HH40, connexin39 was mainly expressed in the ventricular epithelium and three cell layers of the stratum griseum and fibrosum superficialis (SGFS) in the optic tectum, as well as in granular and nuclear cells in the cerebellum. In conclusion, the expression pattern of connexin39 in embryonic nervous system is dynamic. This pattern is different from, and in some aspects complementary to, those showed by other connexins during brain development.

Animals↗
PubMed2006

Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster.

Understanding the genetic architecture of complex traits requires identification of the underlying genes and characterization of gene-by-gene and genotype-by-environment interactions. Behaviors that mediate interactions between organisms and their environment are complex traits expected to be especially sensitive to environmental conditions. Previous studies on the olfactory avoidance response of Drosophila melanogaster showed that the genetic architecture of this model behavior depends on epistatic networks of pleiotropic genes. We performed a screen of 1339 co-isogenic p[GT1]-element insertion lines to identify novel genes that contribute to odor-guided behavior and identified 55 candidate genes with known p[GT1]-element insertion sites. Characterization of the expression profiles of 10 p[GT1]-element insertion lines showed that the effects of the transposon insertions are often dependent on developmental stage and that hypomorphic mutations in developmental genes can elicit profound adult behavioral deficits. We assessed epistasis among these genes by constructing all possible double heterozygotes and measuring avoidance responses under two stimulus conditions. We observed enhancer and suppressor effects among subsets of these P-element-tagged genes, and surprisingly, epistatic interactions shifted with changes in the concentration of the olfactory stimulus. Our results show that the manifestation of epistatic networks dynamically changes with alterations in the environment.

Animals↗
PubMed1997

[The developmental characteristics of the embryonic anlagen of rat neocortex and spinal cord when transplanted into the distal end of the dissected sciatic nerve of adult animals].

The spinal cord and cerebral cortex of 14 day old embryos of Wistar rats were transplanted into the distal stump of the adult rat cut sciatic nerve in order to study dynamics of the development of the transplanted cell elements, and to elucidate relations of neuronal elements in the central and peripheral nervous systems. By means of light and electron microscopy it has been stated that the transplanted nerve cells of the cortex and spinal cord could survive for 60 days and differentiate from neuroepithelial cells and neuroblasts up to young and mature neurons. In the transplants a neuropil is seen to form with both unmyelinated and myelinated axons and synaptic contacts. In the cortex transplants cavities appear paved with ependyma-like cells having cilia and microvilli. It has been found that axons of the transplanted spinal cord neurons may leave transplants to be myelinated by the recipient's Schwann cells of the peripheral nerve.

Animals↗
PubMed2004

Major chromatin remodeling in the germinal vesicle (GV) of mammalian oocytes is dispensable for global transcriptional silencing but required for centromeric heterochromatin function.

Global silencing of transcriptional activity in the oocyte genome occurs just before the resumption of meiosis and is a crucial developmental transition at the culmination of oogenesis. Transcriptionally quiescent oocytes rely on stored maternal transcripts to sustain the completion of meiosis, fertilization, and early embryonic cleavage stages. Thus, the timing of silencing is key for successful embryo development. Yet, the cellular and molecular pathways coordinating dynamic changes in large-scale chromatin structure with the onset of transcriptional repression are poorly understood. Here, oocytes obtained from nucleoplasmin 2 knockout (Npm2-/-) mice were used to investigate the relationship between transcriptional repression and chromatin remodeling in the germinal vesicle (GV) of mammalian oocytes. Although temporally linked, global silencing of transcription and chromatin remodeling in the oocyte genome can be experimentally dissociated and therefore must be regulated through distinct pathways. Detection of centromeric heterochromatin DNA sequences with a mouse pan-centromeric chromosome paint revealed that most centromeres are found in close apposition with the nucleolus in transcriptionally quiescent oocytes and therefore constitute an important component of the perinucleolar heterochromatin rim or karyosphere. Pharmacological inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) revealed that HDACs are essential for large-scale chromatin remodeling in the GV. Importantly, the specialized nuclear architecture acquired upon transcriptional repression is essential for meiotic progression as interference with global deacetylation and partial disruption of the karyosphere resulted in a dramatic increase in the proportion of oocytes exhibiting abnormal meiotic chromosome and spindle configuration. These results indicate that the unique chromatin remodeling mechanism in oocytes may be specifically related to meiotic cell division in female mammals.

Analysis of Variance↗