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PubMed2003

Role of integrins in the development of the cerebral cortex.

Spatial and temporal changes in expression and function of integrin receptors in the developing cerebral wall parallel neurogenesis, radial glial differentiation, neuronal migration and the emergence of neuronal layers in the cerebral cortex. The distinct outcomes of integrin and extracellular matrix ligand mutations underscore the dynamic role they play in these processes during corticogenesis. The changing patterns of adhesive interactions mediated by integrins and their ligands across the cerebral wall during embryogenesis may set in motion developmental programs needed for progressive acquisition of different neuronal or glial phenotypes in the cerebral cortex. Here we discuss the role of integrins during cortical layer formation.

Animals↗
PubMed2004

Development of innovative group work practice using the intervention research paradigm.

Rothman and Thomas' intervention research (IR) paradigm provides an alternative, developmental research method that is appropriate for practice research, especially at the early stages. It is more flexible than conventional experimental designs, capitalizes on the availability of small samples, accommodates the dynamism and variation in practice conditions and diverse populations, and explicitly values practitioners' insights. This article describes two studies to exemplify how the features of IR methodology are well suited to research on innovative group interventions. In one study, a face-to-face psychoeducational group for patients living with sickle cell anemia and chronic depression was used. The other study used an online job stress support group for social workers. The challenges and opportunities that can arise when applying the IR paradigm to develop new interventions are also discussed.

Anemia, Sickle Cell↗
PubMed2002

Transcription factor complex formation and chromatin fine structure alterations at the murine c-fms (CSF-1 receptor) locus during maturation of myeloid precursor cells.

Expression of the gene for the macrophage colony stimulating factor receptor (CSF-1R), c-fms, has been viewed as a hallmark of the commitment of multipotent precursor cells to macrophages. Lineage-restricted expression of the gene is controlled by conserved elements in the proximal promoter and within the first intron. To investigate the developmental regulation of c-fms at the level of chromatin structure, we developed an in vitro system to examine the maturation of multipotent myeloid precursor cells into mature macrophages. The dynamics of chromatin fine structure alterations and transcription factor occupancy at the c-fms promoter and intronic enhancer was examined by in vivo DMS and UV-footprinting. We show that the c-fms gene is already transcribed at low levels in early myeloid precursors on which no CSF-1R surface expression can be detected. At this stage of myelopoiesis, the formation of transcription factor complexes on the promoter was complete. By contrast, occupancy of the enhancer was acutely regulated during macrophage differentiation. Our data show that cell-intrinsic differentiation decisions at the c-fms locus precede the appearance of c-fms on the cell surface. They also suggest that complex lineage-specific enhancers such as the c-fms intronic enhancer regulate local chromatin structure through the coordinated assembly and disassembly of distinct transcription factor complexes.

Animals↗
PubMed2000

Transference and dream in illness: waxing psyche, waning body.

In times of change, crisis, and illness, the excited points of an individual's personal history are reactivated within the transference and may also be noted by observing countertransference. When there are anomalies in the emotional and imaginal circle of the therapeutic relationship, there is occasion for repetition and/or a transformative opening. In some cases, there is simultaneous treatment of severe developmental fixations and compulsions, and issues of individuation. Images may emerge both from the personal field and from the collective and archetypal imagination. These may be expressions of interpersonal experience, intrapsychic dynamics, and physical as well as psychic state.

Chronic Disease↗
PubMed2006

Neural subtype specification from embryonic stem cells.

One of the keys to using embryonic stem cells (ESCs) in brain research and potential application in neurological diseases is directed differentiation of neuronal and glial subtypes. This may be achieved by application of developmental principles in guiding cell lineage specification from naïve stem cells. Establishment of defined ESC differentiation models that recapitulate in vivo development, especially from human ESCs, will most likely provide a dynamic tool for dissecting molecular mechanisms underlying early embryonic development that is otherwise not readily obtainable. This is also a rational and realistic way of producing enriched populations of functional neurons and glia for pathological analyses as well as possible therapeutic applications.

Animals↗
PubMed2005

Neonatal bilabyrinthectomy leads to changes in skeletal muscle fiber form and function.

Children with hypoactive semicircular canals commonly have delayed motor development. We studied ferrets whose vestibular labyrinths were removed at postnatal day 10 (P10) to evaluate 1) development of motor behavior, 2) soleus contractile characteristics, 3) muscle fiber diameter, and 4) the expression of myosin heavy chain (MHC) isoforms. At P30 labyrinthectomized (LAB) ferrets exhibited a significant delay in motor development. At P120, the LAB ferrets continued to have significantly more difficulty with dynamic balance than the SHAM ferrets. At P30, the muscle fibers were about the same diameter as those in the sham operated ferrets (SHAM) at the same age but significantly more developmental MHC isoforms were expressed in the LAB soleus muscle. At P120, both the LAB soleus and medial gastrocnemius expressed significantly more type IIX MHC. The P120 LAB soleus muscle was significantly weaker and the muscle fibers were significantly smaller. These results support the hypothesis that vestibular receptors are important to the development of upright posture and balance activities, and influence muscle fiber development and MHC expression in postural muscles.

Age Factors↗
PubMed1998

Stressors and development: a reciprocal relationship.

In this article we have attempted to delineate the importance of developmental levels in a young person's response to stressors and, conversely, the effect of stressors on levels of development. In so doing, we isolated specific lines of development from their context. We neglected the important roles of rewards and punishments, permissions and prohibitions, family and community dynamics, values, stories and myths. Even in this simplified schema, we have not addressed the importance of protective and risk factors, neither of which are found in isolation; but all of these issues are the subject of articles elsewhere in this issue.

Adolescent↗
PubMed1989

Thyroid function in embryonic and early posthatch chickens and quail.

Technological advances, especially radioimmunoassays, have led to good descriptive information about the timing and pattern of development of the thyroid gland (TG) and circulating thyroid hormone (TH). Immunocytochemical studies in combination with more traditional techniques such as gland ablation and hormone replacement have revealed the time of appearance of each hormone in the axis, the relative amounts of hormone present in each gland at different developmental stages, and a general picture of the pattern of maturation of the hypothalamic-pituitary-thyroid axis. Studies of the pituitary control of the TG remain limited by the lack of adequately specific techniques for measuring avian thyroid-stimulating hormone. Our understanding of peripheral TH dynamics is progressing as a result of iodothyronine deiodinase assays but full understanding will require more elaborate studies that adequately characterize the enzyme system(s) in each case. Molecular techniques have made powerful strides in identifying the gene responsible for producing a protein that appears to be the triiodothyronine receptor. Receptor assays have revealed the pattern of changes in receptor-binding capacities during development but have not yet revealed how binding of hormone to the receptor triggers cellular activity. Molecular genetic techniques are being used to reveal the mechanisms whereby some examples of developmental events (e.g., malic enzyme synthesis) are induced by TH. Although it is not yet possible to assess the value of molecular studies in this area for developing practical applications, these techniques are revealing the fundamental biological roles of TH in growth and development.

Animals↗
PubMed1998

Implications of the spatial and temporal regulation of Hox genes on development and evolution.

Nearly 20 years have passed since Ed Lewis revealed the importance of Hox genes in the specification of different segments in the anterior-posterior axis of the fly. Pioneering studies by several authors, among others Garcia-Bellido and his student Ginés Morata, helped to elaborate a theory of segmental specification that was strengthened with the arrival of molecular techniques to the field of Developmental Biology. The conservation of Hox genes in metazoans at the level of sequence, function and complex organization has resulted in the export of this Drosophila theory as a paradigm to interpret the development of axial specification in organisms less amenable to experimental study. There are two main ways to interpret how Hox genes work in Drosophila. One considering Hox genes as "segment identity" factors giving global properties to the segments in which they are active. Another considering Hox genes as encoding spatially restricted transcription factors required for a number decisions taken at the cellular level. Here I use published and unpublished experimental data to illustrate that early activation of the Hox genes does not establish a gene code that leads to "segment identity". I will stress the point that Hox expression patterns develop with the embryo, that there are many genes involved in this modulation, and that the changing pattern of expression is important to achieve the final shape of the animal. I will show that, by interpreting Hox gene function in this way, some apparently paradoxical results in the Hox field can be answered. Finally, I discuss the implications of dynamic Hox gene expression on the evolution of segment morphology.

Animals↗
PubMed2001

The effect of salinity on different developmental stages of an endemic annual plant, Aster laurentianus (Asteraceae).

Salinity reduces substrate water potential, thereby restricting water and nutrient uptake by plants; salinity may also cause ionic imbalance and toxicity. Because substrate salinity fluctuates through the growing season, a plant may be exposed to different salinity levels, at various stages of development, with potentially significant consequences on population dynamics. Here, we present the results of a study of the effect of substrate salinity on seed germination, seedling emergence, and growth of Aster laurentianus, an annual marsh plant, endemic to the Gulf of St. Lawrence and potentially threatened. Seed germination was reduced in low salt concentration (10 g sea salt/L) and completely inhibited by salinity levels >/=20 g sea salt/L. However, this inhibiting effect was reversible: seeds from the salt treatments germinated readily after being washed in distilled water. Though seedling emergence was diminished at low salinity levels, postemergence survival was little affected. Plant growth was reduced, but net carbon assimilation rate was not affected by high salinity levels. Increased root respiration and respiratory costs associated with salt tolerance might have contributed to lower C accumulation at higher salinity levels. All developmental processes considered are thus negatively affected by substrate salinity, with potentially significant consequences on population abundance and distribution in salt marshes. Yet, the tolerance of this species to high salinity levels after seedling emergence is remarkable. Seed germination represents a major bottleneck in the species life cycle, potentially controlling local distribution and abundance in the natural habitat.

Journal Article↗
PubMed1983

Computer-tomographic investigations in malformations of the occipito-cervical junction.

The diagnosis of occipito-cervical dysplasias has been improved markedly by computer-tomography. Two millimetre transverse cuts with sagittal and coronal reconstructions are necessary. Based on nine cases with nearly all types of malformations it is shown that even complex osseous (mesodermal) malformations and dysplasias as well as isolated or combined neuroectodermal dysplasic or secondary compressive lesions of the medulla oblongata and cord can be detected. Transverse and AP diameters of the foramen magnum and spinal canal and the classical lines and angles can be measured. This time-consuming procedure will give more information than the classical radiological methods and avoid myelographic and cisternal examinations. Its disadvantages are the impossibility of dynamic functional studies and the length of the procedure.

Adolescent↗
PubMed1998

Oxygen, genes, and development: an analysis of the role of hypoxic gene regulation during murine vascular development.

Development of the mammalian cardiovascular system is a complex process guided by both genetic and environmental components. Significant advances in the genetics of vascular development have been accomplished most recently by the analysis of multiple "knockout" and transgenic mice which exhibit varying degrees of impaired vascularity. This review focuses on the potential of the environment of the developing embryo to affect its development. In particular we analyze the evidence implicating the ability of physiological parameters such as oxygen and glucose concentrations within and surrounding the embryo to affect the expression of genes critical for vascular development. We conclude that the vascularization of a developing mammalian embryo is a plastic process dependent on the dynamic interaction between fundamental genetic and physiological factors.

Animals↗
PubMed2000

In situ analysis of RNA and protein expression in whole mounts facilitates detection of floral gene expression dynamics.

UNLABELLED: A three-dimensional whole-mount technique for detection of mRNA and protein expression patterns of floral regulatory genes in inflorescences from Antirrhinum majus is reported. This technique allows the observation of complex expression patterns in situ in developing flowers at different developmental stages initiated sequentially on the same inflorescence and labelled under the same conditions. Thereby, reconstruction from serial two-dimensional sections can be circumvented. The technique was used to study early changes in the expression of DEFICIENS (DEF), a class B floral homeotic transcription factor. Whole-mount analysis revealed that the order of appearance of DEF mRNA and protein expression in the floral primordium is opposite to the order of initiation of organ primordia. As a consequence, stamen primordia express the DEF gene prior to their initiation in whorl three, while petal primordia in the second whorl are morphologically distinct structures when second whorl DEF expression becomes established. This interesting feature was not readily detectable by previous analysis of serial sections. The particular usefulness of in situ analyses in whole mounts is further demonstrated in floral mutants with variable phenotypes and unpredictable sites of aberrant organ development. KEYWORDS: whole mount, in situ hybridization, immunolocalization, Antirrhinum majus, flower development.

Gene Expression↗
PubMed1998

Oncogenes and signal transduction pathways involved in the regulation of Na+ channel expression.

Recent progress in neurobiology has revealed that proteins called 'neurotrophic factors' influence development, maintenance of function, and regeneration of neurons in vertebrate nervous system. These factors include the neurotrophin family, epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), which are expressed in the nervous system. Effects of the neurotrophic factors are mediated through signal transduction pathways in which several cellular protooncogenes play intrinsic roles. Furthermore, studies on mechanisms coupling membrane events to gene activation have demonstrated that transsynaptic input via action potential and neurotransmitters, and membrane depolarization play an important role in the regulation of electrical activities in neurons during and after maturation. Voltage-dependent sodium (Na+) channels mediate an increase in permeability of Na+ during the initial, rapid phase of the action potential in neurons, and are considered to be important determinants of neuronal functions. Their synthesis and expression, therefore, are crucial aspects of neural differentiation and functions. In mammals, an array of functionally distinct Na+ channels arise, at least in part, through transcriptional regulation of the multiple genes that encode distinct Na+ channel alpha subunits (Na alpha). In this review, we discuss the potential roles of the protooncogenes in the nervous system, with particular emphasis on dynamic expression of the Na+ channel gene family.

Animals↗
PubMed1999

Dictyostelium as model system for studies of the actin cytoskeleton by molecular genetics.

The actin cytoskeleton is an essential structure for most movements at the cellular and intracellular level. Whereas for contraction a muscle cell requires a rather static organisation of cytoskeletal proteins, cell motility of amoeboid cells relies on a tremendously dynamic turnover of filamentous networks in a matter of seconds and at distinct regions inside the cell. The best model system for studying cell motility is Dictyostelium discoideum. The cells live as single amoebae but can also start a developmental program that leads to multicellular stages and differentiation into simple types of tissues. Thus, cell motility can be studied on single cells and on cells in a tissue-like aggregate. The ability to combine protein purification and biochemistry with fairly easy molecular genetics is a unique feature for investigation of the cytoskeleton and cell motility. The actin cytoskeleton in Dictyostelium harbours essentially all classes of actin-binding proteins that have been found throughout eukaryotes. By conventional mutagenesis, gene disruption, antisense approaches, or gene replacements many genes that code for cytoskeletal proteins have been disrupted, and altered phenotypes in transformants that lacked one or more of those cytoskeletal proteins allowed solid conclusions about their in vivo function. In addition, tagging the proteins or selected domains with green fluorescent protein allows the monitoring of protein redistribution during cell movement. Gene tagging by restriction enzyme mediated integration of vectors and the ongoing international genome and cDNA sequencing projects offer the chance to understand the dynamics of the cytoskeleton by identification and functional characterisation of all proteins involved.

Actins↗
PubMed2005

Dynamic changes to the inositol 1,4,5-trisphosphate and ryanodine receptors during maturation of bovine oocytes.

The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and ryanodine receptor (RyR) have been identified as two ligand-gated calcium channels which play a critical role in mediating calcium release in many different types of cells and tissues. The physiological significance of the two receptors in regulation of intracellular calcium during meiotic maturation and fertilization in the bovine oocyte was evaluated. Metabolic labeling of bovine oocytes by Met-Cys 35S during early and late maturation was followed by immunoprecipitation of both RyR and IP3R using specific antibodies against these two receptors. Results indicate that IP3R is translated throughout the maturation period; in contrast, RyR is only translated during the late maturation period of bovine oocytes. In addition, the experiments reported here investigate the temporal and spatial relationships between these calcium channels and the endoplasmic reticulum (ER) and cortical granules (CG). Immunocytochemistry, fluorescence staining and confocal microscopy were applied at four oocyte developmental stages: the germinal vesicleintact (GV-intact), metaphase I (MI) and metaphase II (MII) stages of maturation and the fertilized egg at 6 h post insemination (hpi). Although oocytes demonstrated some differences in staining patterns and localization, both receptor types showed apparent dynamic changes during meiotic maturation and dramatic decreases in signals after insemination. These results indicate the changes in the number and distribution of IP3R and RyR may account for the increased intracellular calcium responsiveness at fertilization. The IP3R appears to associate with the ER at the sub-vitelline membrane cortex in bovine oocytes. In addition, RyR appears to associate with the CG. In conclusion, although these two receptors may have different functional roles in regulation of calcium release during meiotic maturation and fertilization, it appears that both IP3R and RyR contribute to the significant increase of intracellular calcium during fertilization and activation in the bovine oocyte.

Animals↗