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Biological effects of a neurotoxic pesticide at low concentrations on sea urchin early development. A terathogenic assay.

Dose-dependent terathogenic effects of an organophosphate insecticide were found during early sea urchin development. This biological assay is low cost, easy to measure, and allows to detect the effects of the exposure of organisms to the active principle at concentrations lower than the acceptable daily intake (ADI) for man. Effects were found independently from the stage of exposure, and were major as earlier exposure occurred. The stronger effects were exerted on the elongation of the skeletal rods, that was easily measured by following the migration of primary mesenchyme cells, labelled by WGA (wheat germ agglutinin).

Animals↗

[Early development of cerebral blood vessels: on the relationship between cerebral histogenesis and internal vascularization].

The purpose of this study is to evaluate the morphological relevance to cerebral histogenesis and internal vascularization during early fetal development of rats. Using light and electron microscopes, fetal brains and spinal cords from embryonic day 11 (E11) to E 16 were observed with special attention to new blood vessel formation in the parenchyma. At stages of the neural groove and neural tube blood vessels were confined in the perineural mesenchyma around the matrix cell layer whose cytoarchitecture was arranged in a pseudostratified pattern and did not include the blood vessels. At the prosencephalic stage (E 13), primordium of the striatum which localized in the ventrolateral portion of the cerebral neopallium made up the migrating zone in outer most of the matrix cell layer and blood vessels firstly appeared in this area. Similarly, the blood vessels were also recognized at the ventro-lateral portion of the mesencephalon where the migrating zone was initially formed on E 13. In the cervical spinal cord, the blood vessels were initially recognized on E 12, when the migrating zone was formed at the area of anterior horn. At the early telencephalic stage during E 14-E 15, blood vessels were evenly distributed in the lateral cerebral neopallium, while the cerebral neopallium in the midline where took place later evolution than lateral neopallium was still remaining in the state of matrix cell layer only, and was also lacking the blood vessels. In this area, first appearance of the vessels was E 15 or E 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacokinetic-pharmacodynamic modelling in the early development phase of anti-psychotics: a comparison of the effects of clozapine, S 16924 and S 18327 in the EEG model in rats.

1. The use of pharmacokinetic/pharmacodynamic (PK/PD) analysis in early compound development was investigated in the rat for two developmental anti-psychotic compounds with clozapine as a positive control. 2. Three plasma samples were collected from each of eight animals according to a pre-defined sampling matrix allowing a total of 12 time points for PK analysis. Quantitative electroencephalography (QEEG), particularly the theta and beta frequencies, was used as a measurement of pharmacological effect. 3. PK/KD modelling of the sparse PK data available relative to a rich set of PD data was achieved using a population approach in NONMEM (IV). Individual PK parameter estimates were incorporated into a PK/PD model. 4. Qualitative EEG changes in rat and human were similar for clozapine, but different for the two developmental compounds, suggesting that changes in these PD parameters may not be specifically related to the anti-psychotic activity. 5. Although no definitive data are available concerning the signal specificity of EEG frequency bands with respect to dopaminergic or serotonergic receptor activity, qualitative and quantitative differences seen in EEG parameters are likely to result from the multiple receptor occupancy for these compounds. 6. The results confirm the value of population PK/PD modelling in conjunction with sparse sampling to enable determination of concentration effect relationships in the pre-clinical development programme of CNS-active drugs.

Algorithms↗

Turkey-chicken hybrids: a cytological study of early development.

Reciprocal hybridization experiments were performed between the line of Beltsville Small White turkeys that has been selected for high incidence of parthenogenesis and two strains of chickens. The eggs were examined cytologically at early stages of development. In the cross of turkey females X chicken males, it was found that both male (2A-ZZ) and female (2A-ZW) zygotes are formed, but the latter are much less viable and usually die in a very early stage of development. Besides the hybrid embryos, parthenogenetic-type embryos also were found. In the cross of chicken females X turkey males, no evidence of successful hybridization was obtained. However, cell division was initiated in 100 percent of the chicken eggs. This fact suggests that turkey sperm had some enhancing effect on parthenogenetic cell division in chicken eggs.

Animals↗

Translocation of a store of maternal cytoplasmic c-myc protein into nuclei during early development.

The c-myc proto-oncogene is expressed as a maternal protein during oogenesis in Xenopus laevis, namely, in nondividing cells. A delayed translation of c-myc mRNA accumulated in early oocytes results in the accumulation of the protein during late oogenesis. The oocyte c-myc protein is unusually stable and is located in the cytoplasm, contrasting with its features in somatic cells. A mature oocyte contains a maternal c-myc protein stockpile of 4 x 10(5) to 6 x 10(5) times the level in a somatic growing cell. This level of c-myc protein is preserved only during the cleavage stage of the embryo. Fertilization triggers its rapid migration into the nuclei of the cleaving embryo and a change in the phosphorylation state of the protein. The c-myc protein content per nucleus decreases exponentially during the cleavage stage until a stoichiometric titration by the embryonic nuclei is reached during a 0.5-h period at the midblastula stage. Most of the maternal c-myc store is degraded by the gastrula stage. These observations implicate the participation of c-myc in the events linked to early embryonic development and the midblastula transition.

Animals↗

trkC-mediated NT-3 signaling is required for the early development of a subpopulation of neurogenic neural crest cells.

Soon after they segregate from the neural tube, trunk neural crest cells disperse on two spatially and temporally distinct pathways. Only crest cells that migrate early and ventromedially give rise to neurons of the peripheral nervous system. It is also known that neural crest cell-derived populations require appropriate environmental cues early in development in order to generate neurons, and for the subsequent survival of differentiated neurons. We examined whether neurotrophin-3 (NT-3), a survival factor for subsets of peripheral neurons, is also involved in the regulation of neurogenesis by neural crest cells. First, we found that premigratory and migrating neural crest cells on the medial migration pathway of Embryonic Day 2.5 (E 2.5) embryos express mRNAs encoding multiple isoforms of the NT-3 receptor, trkC, as do cells in the neural tube and epithelial dermamyotome. On E4, a subpopulation of neurons in nascent sensory ganglia express trkC message. Second, we demonstrate that trkC mRNA is only expressed in neural crest cell populations that possess neurogenic potential. Third, we show that the presence of NT-3, during the initial development of cultured neural crest cells, is required for neurogenesis by a subpopulation of neurogenic neural crest-derived cells. These results suggest that a subpopulation of neurogenic neural crest cells expresses functional trkC receptors and requires the timely availability of NT-3 for their development before reaching their final embryonic locations. We suggest that developmental heterogeneity exists in the identity and requirements of neural crest cell subsets that harbor neurogenic potential. We also suggest that the "paradoxical" expression of trkC receptors by the somitic dermamyotome may, in fact, play a role in the exclusive development of crest-derived neurogenic precursors on the medial pathway by limiting the availability of NT-3 on the lateral pathway.

Animals↗

Development of the glycogen body of the Japanese quail, Coturnix japonica. I. Light microscopy of early development.

The glycogen body is a functionally enigmatic structure located in lumbosacral region of the spinal cord in birds. This tissue is unique to birds, and, although it is believed to be present in all species, studies on the glycogen body to date have been confined largely to the domestic chicken. The present study is the first to describe the glycogen body of the Japanese quail (Coturnix japonica) during incubation and at hatching. Light microscopy and histochemistry were used to identify the glycogen body in the spinal cord of the developing quail beginning at 7 days of incubation and to ascertain the presence of nerve fibers in that tissue at hatching.

Animals↗

[Defects in the prostaglandin system. II. Familial platelet-prostacyclin receptor defect (Wien-Hietzing defect)--pathogenetic significance for (early) development of atherosclerosis?].

A case is reported of a 10 year-old girl admitted to hospital because of severe intermittent claudication. Occlusion of the left popliteal artery was diagnosed. Since successful surgical intervention the patient has been symptom-free. No causative factor was detected for this premature occlusion. During intensive laboratory check-up an extreme diminution in sensitivity of the platelets to prostacyclin and a receptor defect were discovered. This defect seems to be genetically determined. The extent to which this as yet unreported platelet defect might have contributed to the development of atherosclerosis at such an early age is discussed.

Arteriosclerosis↗

Differential expression of sea urchin Otx isoform (hpOtxE and HpOtxL) mRNAs during early development.

Two distinct types of orthodenticle-related proteins (early type: HpOtxE, late type: HpOtxL) of the sea urchin, Hemicentrotus pulcherrimus, have been implicated as enhancer element binding factors of the aboral ectoderm-specific arylsulfatase (HpArs) gene. In order to understand the role of these isoforms during sea urchin development, we have isolated and characterized HpOtx gene. Here we describe the spatial expression patterns of HpOtxE and HpOtxL mRNAs and effects of overexpression of these mRNAs on embryogenesis. Whole-mount in situ hybridization using each isoform-specific probe reveals the complex and dynamic change of expression patterns among three germ layers. HpOtxE mRNA is maternally stored and exists apparently in a nonlocalized manner by the blastula stage. After hatching, HpOtxE transcripts are expressed predominantly in presumptive endoderm cells and gradually decrease during gastrulation. Signals for HpOtxL mRNA are intense at the vegetal half after hatching and subsequently, its expression is restricted to the micromere-derived cells. After primary mesenchyme cell (PMC) ingression, HpOtxL transcripts are localized at the vegetal plate and thereafter, concentrated primarily in ectoderm. Eggs injected with HpOtxE or HpOtxL mRNA develop into similar radialized structures without PMC ingression and gut invagination, whose oral-aboral axes are disrupted. Overexpression of HpOtxE induces accumulation of HpOtxL mRNA at the significantly earlier stages, though HpOtxL overexpression inhibits the accumulation of HpOtxE transcripts. Expression patterns of HpOtxE and HpOtxL in all three germ layers and dramatic morphological changes observed in the mRNA-injected embryos suggest that each HpOtx isoform has an important role in sea urchin embryogenesis.

Animals↗

Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia.

BACKGROUND: Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic transmission has been implicated in schizophrenia. We studied whether transient inhibition of NMDA receptor activity during early postnatal development would produce a behavioral phenotype resembling that of individuals who are susceptible to develop schizophrenia. METHODS: Rat pups were given injections of the NMDA channel blocker MK801 on postnatal days 7 through 10. This period is akin to the prenatal second trimester of primate development. Cognitive function was tested in adulthood. RESULTS: Treatment with MK801 impaired cognitive flexibility and working memory. The impairment in cognitive flexibility was due to increased perseverative behavior. Treatment did not affect locomotor activity or recognition memory. CONCLUSIONS: These results suggest that a brief disruption of NMDA receptors during a sensitive period of cortical development is sufficient to produce selective cognitive deficits that are relevant to schizophrenia.

Age Factors↗

[Morphogenetic function of the nuclei in the early development of the common freshwater snail, Limnaea stagnalis].

The early embryos L. stagnalis were placed in the actinomycin solution at the successive developmental stages. The permeability to actinomycin was previously increased by the pricking through egg capsules. The inactivation of nuclei by actinomycin up to the stage of 12 blastomeres resulted in the arrest of development at the 22 cell stage. The inactivation of nuclei at the subsequent development stages resulted in the developmental arrest at later stages. These data suggest that the embryonic development up to the 22 cell stage is provided by the nuclear function during oogenesis. The morphogenetic nuclear function of the embryo begins at the stage of 12 blastomeres and provides the embryonic development beyond the 22 cell stage.

Animals↗

Isolation of a family of Drosophila POU domain genes expressed in early development.

The POU domain is a approximately 140 amino acid domain shared by several mammalian transcriptional activators. We have isolated genomic and cDNA clones from three Drosophila POU domain genes, designated pdm-1, pdm-2, and Cf1a. All three genes encode a conserved POU-specific domain and a POU homeo domain but are otherwise divergent. By Northern analysis, all three of the genes are expressed in early embryos; the pdm-1 and Cf1a genes are also expressed at lower levels throughout development. The spatial expression patterns of the pdm-2 and Cf1a genes show that they probably play multiple roles during development: an early role in specific ectodermal cells, and a subsequent role in the embryonic nervous system.

Amino Acid Sequence↗

The effect of ethanol upon early development in mice and rats. III. In vivo effect of acute ethanol intoxication upon implantation and early postimplantation stages in mice.

Female albino mice (RAP strain) were injected intravenously with absolute alcohol diluted aa by a.d., on days 2, 3 and 4 of pregnancy respectively. Macroscopically pregnant and empty uteri were controlled by microscopic examination. The developmental rate of postimplantation embryos was controlled by a previously reported biometrical method. The acute ethanol intoxication did not influence the postimplantation developmental rate (except for the appearance and development of the allantoic bud). In some of the uteri of the treated females (mainly of those treated on day 4), free blastocysts were found in the uterine lumen on day 9 of pregnancy, supposedly due to the deleterious effect of ethanol intoxication on central and local factors of implantation. Regressive changes of the decidua and consecutive embryonic death found in two litters may be caused by the same deleterious effect or (and) by inflammatory changes present in the endometrium of some control and treated females. The acute ethanol intoxication lowered the mean litter size in all the experimental groups.

Animals↗

Early development of cerebellar afferent systems that contain corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) and CRF binding sites have been described in the cerebellum of several species, including the North American opossum (Didelphis marsupialis virginiana), the species used in the present study. Inotophoretic application of this peptide in the adult cerebellum enhances the spontaneous and amino acid-induced firing rate of Purkinje cells and overcomes the GABA-induced suppression of Purkinje cell activity. The present account provides immunohistochemical evidence for the localization of CRF in the North American opossum within developing axons and their growth cones prior to the formation of the Purkinje cell and granule cell layers. CRF mRNA is present on postnatal day (PD) 1 within the internal migratory stream of the ventral lateral medulla, which contains migrating olivary neurons, and within the ventral medulla in the region, where inferior olivary neurons first aggregate to form the inferior olivary complex. The olivary complex can first be identified on PD2 and is well defined by PD3. CRF-immunoreactive axons are evident within the cerebellar primordium on PD4 and penetrate the nascent Purkinje cell layer between PD14 and PD26. By PD26, CRF-immunoreactive puncta are organized within the Purkinje cell layer as parasagittal bands. Thus, olivary neurons express CRF mRNA prior to the time that the first CRF-labeled axons are present in the cerebellar anlage (PD4), suggesting that olivary axons are among the first to reach the developing cerebellum. Coincident (PD1-3) with the early transcription of CRF mRNA in the inferior olive, cells in the medullary reticular formation (PD1) and locus coeruleus (PD2) also transcribe CRF mRNA. These brainstem sites also could provide CRF-immunoreactive axons to the developing cerebellum; however, based on the results of this study and correlative data reported in the literature, we propose that the primary source of early-arriving CRF fibers is the inferior olivary complex. The early arrival of CRF-containing axons in the cerebellum prior to synaptogenesis and migration of both granule cells and Purkinje cells suggests a role for this peptide in target recognition and synaptic organization.

Afferent Pathways↗

Early development of the chick embryo.

The ultrastructure of the early chick embryo was investigated, using scanning (SEM) and transmission electron microscopy (TEM). Eggs were obtained from the shell gland by injecting hens intravenously with a synthetic prostaglandin or arginine vasopressin. Embryos were examined during late cleavage (stages IV-VI, Eyal-Giladi and Kochav, '76), formation of the area pellucida (stages VII-XI), and formation of the hypoblast (stages X-XIV). SEM highlighted the reduction in cell number at the underside of the embryo during formation of the area pellucida although it became apparent that the thickness of the embryo is not reduced to a single layer of cells at stage X. In addition, blastomeres at the perimeter of embryos (stages V-VI) project filopodial extensions onto a smooth membrane that separates the sub-embryonic cavity from the yolk. During hypoblast formation, epiblast cells generate stellate projections at their basal aspect, thus providing a meshwork for the advancing secondary hypoblast cells. By stage XII the epiblast was one cell thick and reminiscent of a columnar epithelium when viewed transversely. Cells of the deep portion of the posterior marginal zone were distinguished morphologically in the stage XII embryo by their many cell surface projections and ruffled appearance. Blastomeres at the perimeter of stage V-VI embryos projected filopodial extensions onto a smooth membrane which separates the sub-embryonic cavity from the yolk. This membrane is presumed to be confluent with the cytolemma. Evidence is presented demonstrating the presence of intracellular membrane-bound droplets which are hypothesised to contain sub-embryonic fluid.

Animals↗

Insulin alters cell proliferation during the early development of rodent kidney.

The effects of insulin on early differentiated 15-day fetal mouse kidneys were assessed using an organotypic culture system. High concentrations (30 to 125 mU/ml) of the hormone drastically reduced (50%) the incorporation of 3H-thymidine in replicating cells without affecting either differentiation of forming nephrons or epithelio-mesenchymal relationships. When compared to insulin-like growth factor-I or the potent phorbol ester PMA, the action of insulin seemed to specifically deregulate some components of the transductional machinery controlling cell proliferation. This is opposed to the previous demonstration of a positive influence of insulin on cell proliferation in the human fetal kidney. The results suggest that the common definition of insulin as a fetal growth promoter may depend on the developmental stage of each organ, particularly for the mammalian kidney.

Alkaline Phosphatase↗

[Localization of embryonal acetylcholinesterase during the early development of the chick embryo].

The presence of "embryonic" acetylcholinesterase activity, as described by Drews (1975) was investigated during early chick embryonic development, mainly in the following systems: a) primitive streak and Hensen's node during gastrulation movements; b) area opaca during blood islets and vessels differentiation; c) mesoderma of lateral laminae, during delamination movements. The demonstration of enzymic activity was performed with slightly modified histochemical methods. The enzyme was thus localized around the nuclei, in the cytoplasm and associated to plasma membrane of cells engaged in morphogenetic movements. The enzyme activity localized at the plasma membrane was supposed to be involved in the regulation of membrane functions concerning intercellular communications, such as inductive message, perhaps mediated by ion fluxes.

Acetylcholinesterase↗

Patterns of expression of a 15K beta-D-galactoside-specific lectin during early development of the avian embryo.

We have determined, by immunohistochemical and biochemical techniques, the distribution of an endogenous beta-D-galactoside-binding lectin between the early primitive streak stage and the 5th day of embryonic development of the chick. The lectin, which was purified from the pectoral muscle of 16-day-old chick embryos, migrates on SDS-PAGE as a single polypeptide of relative molecular mass 15 x 10(3). Antibodies to this pure lectin interact with the 15K (K = 10(3) M(r)) polypeptide as well as with a 6.5K polypeptide; this second component appears to be antigenically related to the 15K lectin, as antibodies affinity purified on the 15K band recognize both polypeptides. In early stages of development, lectin immunoreactivity was present in most cells of the epiblast and hypoblast in the region of the primitive streak, while towards the edge of the area pellucida the epiblast was stained less intensely. During gastrulation, strong immunoreactivity was present also in migrating cells and in the mesoblast, while at the margin of the area pellucida the epiblast was negative. Up to the 10-somite stage, lectin immunoreactivity was present in the somites, neural tube and presumptive cardiac region; the non-neural ectoderm and the extracellular matrix were not labeled; the predominant immunoreactive component at this stage of development was the 6.5K polypeptide. Later in development, the lectin immunoreactivity gradually disappeared from the dermamyotome and nervous system to reappear conspicuously as soon as a differentiated myotome could be detected. Immunoreactivity was very high in the myotome, skeletal and cardiac muscles and transient in smooth muscles. The only region of the nervous system that continued to express the lectin throughout development was the trigeminal (semilunar) ganglion; in all regions of the nervous system, the lectin immunoreactivity disappeared early in development to be re-expressed only much later. The lining epithelium of the digestive tract and other endodermal derivatives expressed the lectin transiently. In the extraembryonic membranes, immunoreactivity to the lectin was observed in the yolk sac and in both layers of the amnion. The striking regulation of the expression of this endogenous lectin suggests that its functions are linked to cell proliferation and/or to the selective expression of a developmentally-timed cell phenotype.

Animals↗