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Characterization of Xenopus RalB and its involvement in F-actin control during early development.

We describe the characterization and a functional analysis in Xenopus development of RalB, a small G protein. RalB RNA and protein are detectable during oogenesis and early development, but the gene is expressed only weakly in adult tissues. The RalB transcripts are processed by poly(A) extension during oocyte maturation and up to the gastrulation stage. Microinjection of wild-type or mutant RalB RNAs was performed in fertilized eggs in order to gain insight into the function of RalB during development. We show that during cleavage stages the activated GTP form of RalB specifically induces a cortical reaction that affects the localization of pigment granules. The use of different drugs suggests that this reaction is dependent on the outer cortical actin array. The relation between F-actin and RalB was shown by confocal analysis. Injection of mRNAs encoding the mutated activated form of RalB leads, at dependent doses, to a blocking of gastrulation or defects in closing of neural folding structures. In contrast, the inactivated form blocks only the closing of neural tube. Altogether, these observations suggest that RalB is part of a regulatory pathway that may affect the blastomere cytoskeleton and take part in early development.

Actins↗

Early development of the human area postrema and subfornical organ.

The first appearance and early development of two circumventricular organs, the area postrema (AP) and the subfornical organ (SFO), were investigated in human embryos and fetuses from the 4th to the 40th gestational weeks (GW). The AP appears very early in development, during the GW 10; its high vascularization can be seen from GW14, and differentiated neurons are observed from GW 16. The SFO is characterized by a late onset of development. It can first be distinguished at GW 17, but it does not attain cytological differentiation until the last weeks of gestation. It is suggested that the AP has important functions during fetal life, which are related to normal fetal weight and growth; in contrast the SFO, which is connected with drinking behavior and salt/water balance, seems to play a less essential role in early fetal life.

Body Weight↗

Changes in the nuclear lamina composition during early development of Xenopus laevis.

Changes in protein composition of the nuclear lamina were monitored during early development in Xenopus. Lamin LIII, the only lamin present in oocyte nuclei, serves as a lamin pool for the formation of pronuclei and early cleavage nuclei. It is present in embryos up to the tail bud stages. Lamins LI and LII, the lamins originally found in adult cell nuclei, appear at characteristic times in development. LI first appears at the midblastula transition (MBT), and LII at the gastrula. Tryptic peptide analysis revealed that all three lamin forms found in the embryo are identical with the adult lamins. De novo synthesis of LIII and LI, observed at MBT, is independent of transcription and must therefore be due to activation of maternal mRNAs. These results are discussed in relation to other nuclear changes occurring during early development.

Animals↗

Fertilization and early development of sea urchins.

Scanning electron microscopy (SEM) has been successfully employed for the study of several surface-mediated events during fertilization and early development in sea urchins. In addition to basic morphological descriptions of the sperm, the extrusion of the acrosomal process has been documented with SEM. During sperm incorporation, short microvilli are found to elongate around the successful sperm. In eggs denuded of vitelline layers, in which the elevation and hardening of this fertilization coat is prevented, numerous long microvilli have been shown to cluster around and elongate over the entering sperm during sperm incorporation. Following sperm incorporation and the elevation of the fertilization coat, scanning electron microscopy has been utilized to study the bursts of elongation of the previously short egg microvilli. These microvilli appear to undergo two bursts in length due primarily to the new assembly of microfilaments in the egg cortex. Cytokinesis occurs shortly after the second burst of microvillar elongation. The morula stage is characterized by loosely attached cells which become more closely apposed in subsequent cell divisions to result in the hollow blastula. The ciliated blastula hatches from the fertilization coat, whereupon gastrulation occurs, resulting in a free-swimming, feeding larval stage. This paper reviews the surface alterations and the contribution of scanning electron microscopy to the study of these surface alterations, from fertilization through early development.

Acrosome↗

Awareness of inner experience: a systems perspective on self-regulatory process in early development.

This brief synopsis of an organizational perspective on early development represents an integration of three major areas of the author's research: that of a detailed observational study of early mother-infant interaction over the first three years of life; that of a continuous neonatal state and caregiving interactional monitoring method over the first two months of life; and that of a 25- to 30-year follow-up on the same infants observed initially. From these data a ground plan is proposed for our thinking about the individual's life span trajectory as a unique construction within a unique context for that individual's interactional and adaptive self-regulatory strategies. Beginning with a review of biological principles, the paradoxical integration of complexity and unity in living systems is traced from the conceptualization of infant state and observations on its regulation through the role of state in the origins of awareness of inner experience, to the consolidation and validation of the self as agent in self-regulation. Central to integration is the recognition process, stemming from one's awareness that another is aware of what one is aware of within oneself. The constructionist perspective on the critical role of specificity in this organizing process is illustrated by reference to the negotiation between caregiver and infant of seven issues of adaptive coordination over the first three years of life. Finally, five propositions are formulated describing such specificity in this organizing process, as one that underlies integration of levels of the living system relating the biological, the developmental, the shaping of the life span trajectory, and the reconstructive therapeutic process.

Awareness↗

The early development of the lymphatic system in mouse embryos.

The early development of the lymphatic system was studied in embryos of an inbred strain of the laboratory mouse. During the first stage of its development the system is represented by a more or less regular series of small and blind-ending outgrowths of the major embryonic veins which develop in a cranio-caudalward direction from the jugular to the pelvic region. As a result of differences in growth rates of adjacent anatomical structures this series of early lymphatic primordia becomes subdivided into 4 singular primordia and 12 groups of primordia. After the constituents of each group of early primordia have fused, 16 isolated lymphatic plexuses (sacs) are formed of which 14 are in bilaterally symmetric and 2 are in a median line position: i.e. bilaterally: (1) the jugulo-axillary lymph sac situated lateral to the anterior cardinal vein and dorsal to the primitive ulnar vein and its major branch, the external mammary vein, (2) the paratracheal lymph plexus situated medial to the anterior cardinal vein, (3) the internal thoracic lymph plexus situated lateral to the thoracic part of the posterior cardinal vein, (4) the thoracic ducts situated medial to the thoracic part of the posterior cardinal vein, (5) the lumbar lymph plexus situated dorso-lateral to the abdominal part of the posterior cardinal vein, (6) the subcardinal lymph plexus and (7) the iliac lymph plexus situated ventro-lateral to the abdominal part of the posterior cardinal vein; and in the median line: (8) the subtracheal lymph plexus situated at the confluence of the pulmonary veins and (9) the mesenteric lymph plexus situated near the confluence of the splenic and the superior mesenteric veins. Except for some openings at the jugulo-subclavian confluence all connections with the veins disappear. From the primordia extensions grow out centrifugally. They invade the surrounding tissues and, in part, fuse with similar sprouts of adjacent primordia. In this way a continuous system of lymph truncs is formed that opens into the venous system at the jugulo-subclavian confluence.

Animals↗

[Can meniscus refixation prevent early development of arthrosis in the knee joint? Long-term results].

This retrospective study presents the long-term results after meniscal repair with emphasis on early-development of osteoarthritis in the knee. From 1984 to 1996 meniscal repair using the inside-out technique was performed on 54 patients. 25 patients had an isolated tear of the meniscus and 29 additionally a tear of the anterior cruciate ligament (ACL, combined injury). 18 patients of those with a combined injury showed a stable knee during clinical follow-up. A separate evaluation of this group was carried out. The mean follow-up was 6.4 years. 22 patients were examined over a period of 2-5 years (mean 3.5) after surgery, 32 patients after 5 years (mean 8.9). The clinical evaluation was carried out using IKDC, Tegner activity scale, Lysholm, and Tapper and Hoover-Score as well as the Fairbank radiographic evaluation. According to the Fairbank's evaluation the results show that up to 5 years after meniscal repair only minimal radiographic changes were detectable. In only 21% of patients with an isolated meniscal lesion and in 13% of those with a stable knee after a combined injury beginning of osteorathritic changes were noted more than 5 years postoperatively. Early osteoarthritic changes were present within 5 years after surgery in non-stable knees (untreated rupture, suturing). Patients with meniscal repair mostly regain their original Tegner activity level and good to very good results in the clinical scores. However, the results clearly indicate that the success of meniscal repair depends on the stability of the knee. Thus, meniscal repair in stable knees is recommended to prevent early development of osteoarthritis.

Adolescent↗

Infant-mother attachment security, contextual risk, and early development: a moderational analysis.

In light of evidence that the effects of attachment security on subsequent development may be contingent on the social context in which the child continues to develop, we examined the effect of attachment security at age 15 months, cumulative contextual risk from 1 to 36 months, and the interaction of attachment and cumulative risk to predict socioemotional and cognitive linguistic functioning at age 3 years, using data from the National Institute of Child Health and Human Development Study of Early Child Care. Results indicated that early attachment predicts both socioemotional development and language skills, but not cognitive functioning as indexed by a measure of school readiness, and that the effect of attachment on socioemotional development and expressive language varied as a function of social-contextual risk. Insecure-avoidant infants proved most vulnerable to contextual risk, not children classified as secure or insecure more generally, although in one instance security did prove protective with respect to the adverse effects of cumulative contextual risk. Findings are discussed in terms of risk and resilience and in light of the probabilistic nature of the relation between early attachment and later development.

Affective Symptoms↗

Early development of self-injurious behavior: an empirical study.

The early development of SIB in young children with developmental disabilities was examined by tracking over an 18-month period 16 school-age children who had recently started to show early SIB. Naturalistic observations were conducted in each child's classroom every 3 months, and the association between early SIB and environmental events was examined. Results showed that for the 4 children whose early SIB had escalated over this period, there was a significant association between early SIB and low levels of social contact across observation points, supporting models of the development of SIB. This association might be considered as a risk marker for the exacerbation of SIB. Implications of this finding for targeting early interventions for SIB are discussed.

Adolescent↗

Early development of Eimeria papillata (Apicomplexa: Eimeriidae) in the mouse.

Early development of Eimeria papillata (Apicomplexa) in the mouse was evaluated using Nomarski interference-contrast and brightfield microscopy. Sporozoite-shaped meronts, which were motile and contained a large posterior refractile body and a smaller anterior refractile body, were observed entering and leaving host cells in the jejunum of an experimentally infected mouse at 26 h post inoculation (HPI). However, early developmental stages were not observed in tissue of the duodenum, ileum, cecum and colon. The mean length and width of these meronts (n = 20) were 12.0 microns and 3.7 microns, respectively. Spherical or subspherical meronts containing crescent-shaped merozoites were observed at 36 HPI.

Animals↗

Two distinct phases characterize maturation of neurons in the nucleus of the tractus solitarius during early development: morphological and electrophysiological evidence.

We have used electrophysiology and light microscopy of intracellularly labeled neurons in the nucleus of the tractus solitarius (nTS) in brainstem slices of the newborn rat (P0 to P6) to examine the functional and morphological correlation of their development. Three-dimensional reconstruction of neurons injected intracellularly with biocytin, following electrophysiological recording, revealed a close correspondence between morphological immaturity (appearing as polarization of the dendritic tree) and the absence of a ramp-like voltage trajectory at the offset of hyperpolarizing current injections-IA negativity (8 of the 8 cells examined showed this correlation). These morphologically polarized IA negative neurons showed preferential dendritic sprouting in two diametrically opposite poles of the perikaryon. The orientation of the polarity differed according to the rostrocaudal location of the neuron. The appearance of a polarized dendritic tree during the first (immature) phase was transient and closely coincident with IA negativity. Following the development of adult-like electrophysiological characteristics, i.e., IA positivity, nucleus of the tractus solitarius neurons showed remarkably different morphological features (9 of 10 cells). These included a wide-spread branching of the dendritic tree in all directions, giving it a bushy appearance (cell body to dendrite ratio of 1:40). Numerous dendritic spines, growth cones on both dendrites and axons, and axon collateralization were present during both phases and indicate that nTS neurons during the two phases of early development demonstrate dynamic features of growth and maturation. The development of adult-like electrophysiological characteristics, i.e., IA positivity, progressively increased in the postnatal period. During the later part of the first postnatal week, twice as many neurons showed IA positivity in days P3 to P6 as compared with days P0 to P2. These results reveal the dynamic nature of neurons in the nTS during early development and illustrate the close link between morphology and functional characteristics in this region. We suggest that the establishment of adult-like morphology can be modified by appropriate environmental clues provided to nTS neurons during the initial (immature) phase of early postnatal development.

Action Potentials↗

Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.

Tumor necrosis factor (TNF) alpha is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune, insulin-dependent type I diabetes. Treatment of newborn female NOD mice with TNF every other day for 3 wk, led to an earlier onset of disease (10 versus 15 wk of age in control mice) and 100% incidence before 20 wk of age (compared to 45% at 20 wk of age in control phosphate-buffered saline treated female mice). In contrast, administration of an anti-TNF monoclonal antibody, TN3.19.12, resulted in complete prevention of IDDM. In vitro proliferation assays demonstrated that mice treated with TNF developed an increased T cell response to a panel of beta cell autoantigens, whereas anti-TNF treatment resulted in unresponsiveness to the autoantigens. In addition, autoantibody responses to the panel of beta cell antigens paralleled the T cell responses. The effects mediated by TNF appear to be highly age dependent. Treatment of animals either from birth or from 2 wk of age had a similar effect. However, if treatment was initiated at 4 wk of age, TNF delayed disease onset. These data suggest that TNF has a critical role in the early development of autoimmunity towards beta-islet cells.

Age Factors↗

Difference in early development of presumed monozygotic twins with Rett syndrome.

Normal early development has generally been insisted on as an essential criterion for the diagnosis of Rett syndrome. A new set of monozygotic female twins is reported. Twin 1 was considered to be abnormal from birth while delay was not suspected in twin 2 until she was about one year old. Some regression occurred during the second year in both twins, who are now clinically indistinguishable from each other at age 4 years. Other than a slight difference in head circumference at birth, no environmental factor which could account for the clinical difference has been identified.

Child, Preschool↗

Early development of efferent projections from the chick tectum.

The early development of the uncrossed tectobulbar and the crossed tectospinal tracts was studied. These two projections arise from the same structure, the mesencephalon, and develop during the same time period, but follow divergent courses. We have traced the pathways followed by these projections and identified the positions at which axon guidance decisions are made. The first neurons differentiate either side of the entire rostrocaudal extent of the dorsal midline and initiate axons that extend dorsoventrally across the surface of the tectum. At the ventral edge of the tectum these axons turn abruptly and fasciculate to form a caudal descending projection to the hindbrain. These axons extend to the caudal hindbrain and do not project to the periphery along cranial nerve roots. We therefore consider this tract to be the tectobular, rather than the mesencephalic division of the trigeminal. While the tectobulbar projection is still developing, a second wave of axons is initiated, which arises from only the rostral part of the tectum. These axons grow beyond the tectobulbar turn point and continue toward the ventral midline, where they cross the floor plate, before turning caudally at the lateral edge of the main descending hindbrain tract, the ventrolateral tract. We discuss the development of these tracts with reference to possible guidance cues mediating their course.

Animals↗

Early development of cochlear hair cell stereociliary surface morphology.

The early development of the surface structures of differentiating cochlear hair cells (guinea-pig) was analysed by scanning electron microscopy (SEM). A basal-to-apical gradient was evident in hair cell maturation. Inner hair cells developed before outer hair cells at the same level in the cochlea. The first sign of the onset of hair cell differentiation was a regularization of the pattern of microvilli on the future hair cell. Later, the cluster of regularized microvilli was rebuilt to form the stereociliary bundle, with a stepwise increase in the length of those stereocilia facing the stria vascularis.

Animals↗

Mitochondrial differentiation during the early development of the brine shrimp Artemia franciscana.

During the early development of Artemia there is an increase in mitochondrial enzyme activities of about one order of magnitude, whereas the activities of two cytoplasmic enzymes tested as controls remain unaltered. The mitochondrial enzyme activation correlates with (i) large changes in mitochondrial morphology, (ii) a 5-fold increase in the amount of the H+-ATP synthase beta-subunit and (iii) a dramatic increase in the steady-state level of mitochondrial mRNAs, whereas mitochondrial rRNA concentrations remain mostly unchanged. In contrast, the level of mitochondrial DNA does not change significantly during the first 20 h after resumption of development. After hatching, the mitochondrial DNA content increases twice in parallel with one round of cellular division, thus indicating that mitochondrial and nuclear replication are coupled in Artemia postgastrular development. The data presented strongly suggest that mitochondrial maturation in the absence of significant mitochondrial proliferation is responsible for the dramatic increase in mitochondrial function that takes place after resumption of development in Artemia.

Adenosine Triphosphatases↗