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The early development of the neopallial wall and area choroidea in fetal rats. A light and electron microscopic study.

The telencephalic wall was studied by light and electron microscopy in 11-13 day old fetal rats (E11-13). A few specimens from E14-16 were also included for comparisons. Two areas were selected: the dorso-lateral convexity of the hemispheric vesicles, called the neopallial wall, and the area choroidea, the posterior part of the telencephalic roof which unites the two hemispheres. Our observations and a review of the literature have shown that on E11-12 the neopallial wall, the telencephalic roof, and the hippocampal anlage between them form a continuous, nonstratified, cohesive monolayer of columnar and mitotic cells, which essentially is similar to epithelial monolayers elsewhere in the body. This simple structure is modified late on E12 or early in E13 in the neopallial wall when postmitotic neurons appear and migrate in order to form the cortical plate. However, bipolar radially oriented cells, which span the entire width of the wall, still predominate. These cells, now called radial glial cells, increase greatly in number and length during the period of neuronal migration. The cuboidal cells in the neural tube, the columnar cells in the early neopallial wall, and the radial glial cells in the period of neuronal migration have the same basic structure. They are axially polarized epithelial cells which are characterized by the following basic features. They have an elongated bipolar shape which is maintained by a cytoskeleton of longitudinally oriented microtubules. Opposite ends are different structurally and functionally. Thus, the apical ends, connected by tight junctions, face the fluid-filled cavity while the outer ends, covered by a basal lamina, face mesenchymal tissue including blood vessels. A polarization of cytoplasmic organelles is also evident, e.g. the Golgi apparatus has always a supranuclear position. During the early development of the telencephalon this basic epithelial structure is maintained but is modified locally in order to serve various functions. The columnar/radial glial cells in the neopallial wall are elongated and slender, have a narrow Golgi apparatus, profiles of RER and vesicles, relatively few ribosomes, and show a few examples of micropinocytosis. These cells grow continuously in length during development. On the other hand, the cells in the area choroidea have a low columnar or cuboidal shape, which does not change during development. The inner portion (between the nucleus and the ventricle) contains a voluminous Golgi apparatus, many mitochondria, RER cisternae which contain electron-dense material, SER, and many vesicles. The inner ends of the cells project into the ventricular cavity as bulbous or apical protrusions which contain many organelles, especially MVBs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Gamma-aminobutyric acid agonist-induced alterations in the ultrastructure of cultured cerebellar granule cells is restricted to early development.

The effect of 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) on the ultrastructural composition of cultured cerebellar granule cells was investigated during development by quantitative electron microscopy (morphometric analysis). Granule cells were exposed to THIP (150 microM) for 6 h after 7 and 14 days, respectively, in culture. THIP treatment of 7-day-old cultures led to a statistically significant increase in the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus, vesicles, and coated vesicles, whereas no significant increase in the cytoplasmic density of these organelles was observed in 14-day-old cultures exposed to THIP for 6 h. These findings show that the effect of THIP on the ultrastructural composition of cultured cerebellar granule cells is restricted to early development.

Animals↗

The axr6 mutants of Arabidopsis thaliana define a gene involved in auxin response and early development.

The indolic compound auxin regulates virtually every aspect of plant growth and development, but its role in embryogenesis and its molecular mechanism of action are not understood. We describe two mutants of Arabidopsis that define a novel gene called AUXIN-RESISTANT6 (AXR6) which maps to chromosome 4. Embryonic development of the homozygous axr6 mutants is disrupted by aberrant patterns of cell division, leading to defects in the cells of the suspensor, root and hypocotyl precursors, and provasculature. The homozygous axr6 mutants arrest growth soon after germination lacking a root and hypocotyl and with severe vascular pattern defects in their cotyledons. Whereas previously described mutants with similar developmental defects are completely recessive, axr6 heterozygotes display a variety of morphological and physiological alterations that are most consistent with a defect in auxin physiology or response. The AXR6 gene is likely to be important for auxin response throughout the plant, including early development.

Arabidopsis↗

Early development of subcortical regions involved in non-cued attention switching.

This study examined the cognitive and neural development of attention switching using a simple forced-choice attention task and functional magnetic resonance imaging Fourteen children and adults made discriminations among stimuli based on either shape or color. Performance on these trials was compared to performance during blocked trials requiring all color or all shape discriminations. Magnetic resonance echo planar images were acquired during performance of the task. Both children and adults showed robust bilateral activity of the caudate nucleus when switching attention between color and shape discriminations that correlated negatively with mean response latency on these trials. However, neither switching costs nor caudate activity correlated with age, suggesting early development of the underlying neural circuitry involved in switching between salient stimulus sets. Overall, children and adults differed in performance and patterns of brain activity on the task, with adults responding more accurately and faster than children, and recruiting more prefrontal and parietal regions. These results suggest an important role of subcortical regions (i.e. caudate nucleus) in non-cued attention switching, with increasing recruitment of cortical regions with age.

Adolescent↗

Natural killer cell activity in patients with hepatocellular carcinoma relative to early development and tumor invasion.

To evaluate the significance of natural killer (NK) cell activity in the clinical assessment of patients with hepatocellular carcinoma (HCC), 32 patients combined with liver cirrhosis (LC) and HCC, and 29 LC patients were studied. The NK cell activity was markedly decreased in HCC patients and the LC group as compared with the control group, but there was no statistical difference between the NK cell activity of the HCC group and the LC group. The depression of NK cell activity in HCC patients was inversely correlated with the patient's age, and the HCC patients with venous invasion or with both lobes involved had lower NK cell activity. These results suggest that the decreased NK cell activity in HCC patients might be related to the coexistent liver disease, and marked decrease in NK cell activity might be one of the causes for the early development and invasion of HCC.

Adult↗

Effect of maternal adrenalectomy and corticosterone therapy on the early development of B-cells in the fetal pancreatic islet in the rat.

Pregnant Wistar rats were divided into 3 groups, non-operated control, adrenalectomized, and adrenalectomized and corticosterone-treated. Maternal adrenalectomy was performed on day 6 of gestation. Corticosterone therapy was made from the day at operation to the day at observation. The growth pattern of insulin-producing B-cells was observed immunohistochemically and histometrically from days 12 to 16. The results obtained were as follows: From day 12 to day 15, maternal adrenalectomy resulted in a significant retardation of the growth of insulin-positive B-cells in terms of the collective volume of the cells. Maternal corticosterone therapy prevented this retardation. On day 16, however, the growth of B-cells in collective volume overcame the suppressive effect of maternal adrenalectomy. These results suggest that the lack of adrenocortical hormones causes a retardation of B-cell growth in early development, and that, when once developed well, B-cells can grow independently of the hormones.

Adrenalectomy↗

The early development of the atrioventricular node and bundle of His in the embryonic chick heart. An electrophysiological and morphological study.

The development of the atrioventricular node and bundle of His of embryonic chick hearts was studied by electrophysiological and morphological techniques. The dorsal wall of the AV canal and the interatrial septum were explored to determine if they contribute to the formation of the AV node and bundle of His. The resting membrane and action potentials of the interatrial septum cells were systematically analyzed and found to undergo progressive differentiation with development. The earliest identification of the AV node and upper bundle of His group of cells was achieved at 5 1/2-6 days of development by the electrical recording of their corresponding characteristic action potentials, from a circumscribed area located in the lowest and dorsal segment of the interatrial septum. The morphological and anatomical characterization of the cells was made following electrical recording and labelling with charcoal particles. The earlier AV node and bundle of His responses had similar characteristics to those of the adult heart. It is concluded that the AV node and upper bundle of His cells derive from the low interatrial septum. The possibility that AV canal cells contribute to this event was discarded. The functional relationship of the Av node and bundle of His with other cardiac tissues during the early development of the heart is discussed.

Animals↗

Maternal adrenocortical hormones maintain the early development of pancreatic B cells in the fetal rat.

To investigate the effect of maternal adrenocortical hormones on the development of fetal pancreatic islet cells, pregnant rats were adrenalectomised on d 6 of gestation. On d 12-16 the growth patterns of fetal insulin-producing B cells, glucagon-producing A cells, and somatostatin-producing D cells were observed histometrically. Maternal adrenalectomy resulted in growth retardation of fetal B cells on d 12-15. Maternal corticosterone therapy prevented this retardation. Maternal adrenalectomy, however, did not affect the developmental patterns of A and D cells. By Western blotting and immunohistochemistry, glucocorticoid receptors were demonstrated to be present in the islet cells from d 12 to d 15. These results suggest that maternal adrenocortical hormones, glucocorticoids in particular, maintain the early development of fetal pancreatic B cells through their specific intracellular glucocorticoid receptor.

Adrenal Cortex Hormones↗

Expression of ISWI and its binding to chromatin during the cell cycle and early development.

We have characterized Xenopus ISWI, a catalytic subunit of a family of chromatin-remodeling complexes. We show that ISWI is expressed constitutively during development but poorly expressed in adult tissues except oocytes which contain a large store of maternal protein. We further analyzed its localization both in vivo and in vitro in Xenopus cell cycle extracts and identified that ISWI binds to chromatin at the G1-S period. However, its association to chromatin does not require ongoing DNA replication. Immunodepletion of ISWI has no effect on either sperm chromatin decondensation or the kinetics and efficiency of DNA replication. Nucleosome assembly also occurs in ISWI-depleted extracts, but nucleosome spacing is disturbed. From these results, we conclude that ISWI is not necessary for sperm chromatin decondensation and the accelerated rates of DNA replication that characterize early development.

Adenosine Triphosphatases↗

Xenopus cyclin D2: cloning and expression in oocytes and during early development.

We have isolated and characterized a cDNA which contains the entire coding sequence of Xenopus laevis cyclin D2 protein. Cyclin D2 mRNA is identified as a member of the class of maternal RNAs. It is rare and stable during embryonic development at least until tadepole. In addition, a second cDNA coding for a truncated version of cyclin D2 was also isolated. Microinjection of cyclin D2 into oocytes undergoing meiotic maturation and parthenogenetic activation reveals that the protein is stable for several hours, independently of the ubiquitin-mediated degradation of cyclin B2 that takes place periodically during this process. Microinjected cyclin D2 localizes both in the cytoplasm and in the nucleus of oocyte. In somatic cells, it is well established that cyclin D2 is almost exclusively nuclear and very labile. The unusual behaviour of cyclin D2 upon injection into oocytes may provide indications about a possible role for this protein during meiosis and early development.

Amino Acid Sequence↗

Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3 signaling pathway reveal a role in early development.

GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed.

Animals↗

The nuclear-cytoplasmic distribution of the Xenopus nuclear factor, xnf7, coincides with its state of phosphorylation during early development.

We describe the characterization in Xenopus laevis of a nuclear protein, xnf7, which is first detected in the oocyte GV and is eventually enriched in nuclei of cells of the adult brain. Previous studies have shown that this protein contains zinc-finger-like structures and acidic domains typical of transcriptional activators, and is phosphorylated in vitro by p34cdc2 protein kinase. The protein also binds to double-stranded DNA. These data suggest that xnf7 may function as a transcription factor. During oocyte maturation, xnf7 is released into the cytoplasm and is not detectable in nuclei until the mid-blastula-gastrula stage of development. Western blot analysis of xnf7 isolated from oocytes and eggs showed the existence of multiple bands or isoforms of the protein. Unique isoforms that are generated during oocyte maturation are the result of phosphorylation. The phosphorylated isoforms remain in the cytoplasm until the mid-blastula stage. The re-accumulation of protein in the embryonic nuclei at this time correlates with the increase in abundance of the less phosphorylated isoforms. The xnf7 protein possesses a nuclear localization signal (NLS) similar to the bipartite signal found in nucleoplasmin. Newly synthesized xnf7 accumulated in the oocyte GV to detectable levels within a few hours following synthesis suggesting that retention of the protein in the cytoplasm during early cleavage may be due to a process that interferes with the function of the NLS. These data suggest that compartmentalization and/or post-translational modification of the nuclear protein xnf7 may be involved in regulating its function during early development.

Animals↗

Probing the program of gene expression utilized in early development.

Somatic cell nuclei injected into amphibian oocytes enlarge, exchange protein with the surrounding cytoplasm, and actively synthesize RNA for weeks. The message activity of the RNAs synthesized within the oocytes can be detected as new proteins made a few days after the injection of somatic nucleic. The oocyte cytoplasm seems to reprogram the injected nuclei, allowing the expression only of those genes which are normally active in oocytes (De Robertis and Gurdon, 1977). Genes which are unexpressed in somatic cells can be activated by injecting Xenopus laevis somatic nuclei into oocytes of Pleurodeles waltlii (Urodela). The genes that were activated are normally expressed in Xenopus oocytes but not in somatic cells. Conversely, genes which are normally expressed in somatic cells but not in oocytes become inactive after injection into oocytes. We conclude that genes which become inactive during cell differentiation can be reactivated, in the absence of cell division, by normal components of oocyte cytoplasm. These components could turn out to be examples of the "determinants" of egg cytoplasm responsible for nuclear activity in early development.

Animals↗

Validation of the human ozone challenge model as a tool for assessing anti-inflammatory drugs in early development.

This study aimed to test the utility of the ozone challenge model for profiling novel compounds designed to reduce airway inflammation. The authors used a randomized, double-dummy, double-blind, placebo-controlled 3-period crossover design alternating single orally inhaled doses of fluticasone propionate (inhaled corticosteroids, 2 mg), oral prednisolone (oral corticosteroids, 50 mg), or matched placebo. At a 2-week interval, 18 healthy ozone responders (>10% increase in sputum neutrophils) underwent a 3-hour ozone (250 ppb)/intermittent exercise challenge starting 1 hour after drug treatment. Airway inflammation was assessed at 2 hours (breath condensate) and 3 hours (induced sputum) after ozone challenge. Compared to placebo, pretreatment with inhaled corticosteroids or oral corticosteroids resulted in a significant reduction (mean [95% confidence interval]) of sputum neutrophils by 62% (35%, 77%) and 64% (39%, 79%) and of sputum supernatant myeloperoxidase by 55% (41%, 66%) and 42% (25%, 56%), respectively. The authors conclude that an optimized ozone challenge model (including ozone responders and ensuring adequate drug levels during exposure) may be useful for testing novel anti-inflammatory compounds in early development.

Administration, Inhalation↗

A novel TBP-interacting zinc finger protein functions in early development of Xenopus laevis.

A zinc finger protein that interacts with Xenopus TATA-binding protein was previously isolated by a yeast two-hybrid screen and found to serve as a transcriptional repressor. The gene was designated the negatively regulating zinc finger protein gene (NZFP). Herein, NZFP was found to be expressed maternally. After gastrulation, the level of NZFP mRNA decreased significantly throughout the neurula stage. However, mRNA levels increased at stage 35 and then began to decrease at stage 48. Eventually, no NZFP mRNA was observed in adult tissues except in the ovary. NZFP mRNA was detected in the animal hemisphere during gastrulation and observed in the neural ectoderm at the neurula stage. At the tailbud stage, NZFP was highly expressed in the head tissues such as brain, eyes, otic vesicles, lateral line placodes, and branchial arches, but weakly in somites. Depletion of NZFP in the embryos using RNA interference caused premature death at the gastrula stage or induced secondary partial axis after gastrulation. These results strongly suggest that NZFP is an essential transcription factor involved in the cell movement during gastrulation and the formation of the dorsal axis during early development in Xenopus.

Amino Acid Sequence↗

Early development of primary biliary cirrhosis in female C57BL/6 mice because of poly I:C administration.

BACKGROUND: Primary biliary cirrhosis (PBC) is one of the organ-specific autoimmune diseases characterized by destruction of the biliary epithelial cells, cholestasis, liver cirrhosis, and liver failure. With the postulation that induction of the autoimmune process might induce PBC-like cholangitis, here we used polyinosinic polycytidylic acid (poly I:C), an inducer of type-1 interferon (IFN), to generate an autoimmune cholangitis animal model. METHODS: Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 28 consecutive weeks. Liver specimens were collected to evaluate the degree of cell infiltration. Autoantibodies, including antimitochondrial antibody (AMA), were assayed by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. IFN-alpha was estimated in the sera by an ELISA method. Poly I:C injection induced IFN-alpha. RESULTS: Mononuclear cells were detected at the portal areas 8 weeks after the start of poly I:C injection, which progressed up to 16 weeks. Autoantibodies, including AMA, were detected in the sera from all poly I:C-injected mice. CONCLUSIONS: In conclusion, we show an early development of a PBC-like cholangitis in a genetically susceptible mouse strain because of poly I:C administration. This model would be helpful to study PBC immunopathogenesis and to evaluate the effectiveness of newly developed therapeutic regimens for PBC.

Animals↗

Differential expression of duplicated genes for brain-type fatty acid-binding proteins (fabp7a and fabp7b) during early development of the CNS in zebrafish (Danio rerio).

A gene for the zebrafish brain-type fatty acid-binding protein (fabp7b) was identified and its structure defined. The zebrafish fabp7b gene spans 1479 bp and consists of four exons encoding 24, 58, 34 and 16 amino acids, respectively, which is identical to the structure of the fabp7a gene previously described. The complete fabp7b cDNA was isolated by 5' and 3' RACE and its nucleotide sequence determined. The deduced amino acid sequence of FABP7B encoded by the zebrafish fabp7b gene shares 82% identity with that of FABP7A encoded by the zebrafish fabp7a gene. A single transcription start site for the fabp7b gene was mapped by 5' RNA ligase-mediated RACE. Phylogenetic analysis indicated that the duplication of the fabp7 genes occurred in the fish lineage after their divergence from mammals. The zebrafish fabp7b gene was assigned to linkage group 20 by radiation hybrid mapping. Reverse transcription-polymerase chain reaction detected fabp7b transcripts in the same adult tissues as fabp7a transcripts. In the brain, levels of fabp7b transcripts were lower than fabp7a transcripts. Whole-mount in situ hybridization showed that the zebrafish fabp7a transcripts were distributed in the early developing central nervous system. In addition to being expressed in the developing brain and retina, zebrafish fabp7b mRNA was also detected in the swim bladder and pharynx during the embryonic to larval transitory phase.

Animals↗

Cell behavior during early development in the South American annual fishes of the genus Cynolebias.

Living embryos of three species of South American annual fishes, Cynolebias constanciae, C. nigripinnis, and C. whitei, were observed from fertilization through the 10-somite stage. A description of normal stages of development applicable to all three species of Cynolebias is presented. Cleavage (stages 1-10) is meroblastic and produces a typical teleost blastoderm. Following cleavage (stages 11-13) blastomeres segregate into two populations, viz., 1) a population of deep blastomeres that will disperse as single motile cells, and 2) a hemispherical shell of outer blastomeres that flattens to form an enveloping cell layer (EVL). When epiboly of the EVL and the yolk syncytial layer (YSL) commences (stage 14), deep blastomeres clump together as a consolidation mass and then migrate outward as single cells on the YSL. When epiboly is concluded (stage 19), deep blastomeres have completely dispersed. If diapause does not intervene, the dispersed phase lasts only a few days. Subsequently, the dispersed cells come together to form a definitive aggregate (stage 27). Embryogenesis within the reaggregated mass of previously dispersed cells produces a typical teleost embryo. Early development in Cynolebias resembles that of other South American annual fishes, such as Austrofundulus, in that a phase of deep blastomere dispersion and reaggregation spatially and temporally separates epiboly from embryogenesis. Several features of development markedly differ from Austrofundulus. There are far fewer (250 vs. 2,500) deep blastomeres. Deep cells of Cynolebias are flattened rhomboids with filipodial extensions in contrast to the amoeboid cells of Austrofundulus. Blastomeres of dispersion and reaggregation stages in Cynolebias send out numerous cell surface extensions onto the YSL and in contact with one another, and often line up in rows as do some African annual fishes, e.g., Nothobranchius. During Dispersion II (stage 21), Reaggregation I (stage 22), and Reaggregation II (stage 23), deep cells move in an oriented pattern with respective mean velocities of 3.48 +/- 0.91, 1.28 +/- 0.46, and 1.31 +/- 0.31 microns/minute. Cells move toward a granular mass of unknown composition, located at the YSL-yolk interface in the lower hemisphere of the egg. This mass appears to coincide with the site of cell reaggregation.

Animals↗