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PubMed2002

Ran GTPase expression during early development of the mouse embryo.

Ran is a small GTP-binding protein involved in several essential roles for cell viability. This observation implies Ran might be ubiquitously expressed during development. However, Ran shows a differentiated expression pattern that is restricted to specific tissues from embryo to adult. At early embryonic stages of mouse development we found persistent Ran expression in proliferating neural tissue, neural crest derived dorsal root ganglions and sensory pits. We also showed an accumulation of Ran transcripts in main embryonic haematopoietic tissues: blood islands first and then hepatic bud. In advanced stages of development Ran is also expressed in other tissues showing a high cell turnover.

Animals↗

PubMed2003

Early development of the olfactory organ in sturgeons of the genus Acipenser: a comparative and electron microscopic study.

Formation and morphology of the olfactory organ of vertebrates has been intensely studied in some taxa for more than a century. As a functionally important and complex sensory organ, its ontogenetic development has often been a matter of debate on higher-level craniate evolution. However, sufficient knowledge of structure and development of the olfactory organ in the crucial taxa needed for a serious phylogenetic reasoning is generally not available. This study aims at this essential primary data source, the detailed structure, morphogenesis, and character definition of the olfactory organ in more basal clades of jawed vertebrates (Gnathostomata). Sturgeon fishes (Acipenseriformes) as recent basal actinopterygians are expected to provide insight into archaic characters and character combinations in bony fishes. Thus, the development of the olfactory placodes of the sterlet, Acipenser ruthenus, and the Siberian sturgeon, Acipenser baerii, was followed histologically, by semi-thin serial sections, and by scanning and transmission electron microscopy. Except for the timing, virtually no differences were observed between the two species. The olfactory placodes become two-layered early in embryonic development. Both the superficial epidermal and the subepidermal layer can easily be distinguished and their development followed by ultrastructural properties. There are three different types of receptor cells: ciliated, microvillous, and crypt cells. The development of the ciliated and the less abundant microvillous receptor cells from the subepidermal layer of the placode is demonstrated. The non-sensory cells of the differentiated olfactory epithelium, i.e. ciliated non-sensory cells and supporting cells, exclusively derive from the superficial epidermal layer. In this respect, acipenserids clearly demonstrate close resemblance to the morphogenetic process found in the tetrapod Xenopus (Anura). The only other adequately described mode found in the actinopterygian zebrafish ( Danio rerio), is considered a derived character. In this case, all cells of the differentiated olfactory epithelium derive from one placodal cell layer. The mode of formation of the nasal sac and its ventilatory openings found in the acipenserids examined here, represents a widespread and probably a plesiomorphic condition of osteognathostomes. In both species, differentiation of the basic cellular composition of the olfactory epithelium is far advanced at the time of onset of extrinsic feeding.

Animals↗

PubMed2002

Effects of iron sulfate dosage on the water flea (Daphnia magna Straus) and early development of carp (Cyprinus carpio L.).

Adult water fleas, Daphnia magna Straus, and the early life stages of carp, Cyprinus carpio L., were exposed to river water near an iron sulfate dosage installation to determine the effects of phosphate precipitation with iron(II)sulfate. Tests were conducted during two consecutive dosage periods of 3,000 and 5,000 kg/day iron sulfate (520 and 620 microg/L total Fe respectively) at the dosage site and at a reference site (60 microg/L total Fe) further downstream. Though survival remained unaffected, the filter-feeding D. magna accumulated iron and other metals at the dosage site. Viability of offspring was strongly reduced at the highest dose of iron sulfate compared to the lower dose and the reference site. Specific staining of microscopic sections revealed a strong accumulation of iron(III) in the digestive tract. The egg membranes of the carp embryos accumulated not only substantial amounts of iron but also other metals, including cadmium and aluminium. Hardly any of the metals passed the egg membranes and reached the embryos. After hatching the accumulation of cadmium by the larvae increased rapidly and iron levels were elevated at the highest dose of iron sulfate, parallel with the onset of exogenous feeding. Iron(III) particles were observed in the intestines at histological examination. In addition, at 620 microg/L total Fe a strong increase in whole-body levels of the stress hormone cortisol was observed in the carp larvae, indicating a physiological response to adverse conditions. The results indicate that the rapid oxidation of free Fe2+ into iron(III) forms and the precipitation of iron(III) into larger particles resulted in a low acute toxicity of the river water directly at the iron sulfate dosage site. The observed chronic and sublethal effects at the dosage site probably resulted from the intestinal uptake of iron(III) and other toxic metals associated with the food particles. However, these effects could no longer be observed at the reference site, 9 km downstream from the dosage site.

Animals↗

PubMed2001

Early development of intractable epilepsy in children: a prospective study.

BACKGROUND: Little is known about early prediction of intractable epilepsy (IE) in children. Such information could help guide the early use of new therapies in selected patients. METHODS: Children with newly diagnosed epilepsy (n = 613) were prospectively identified from child neurology practices in Connecticut (1993--1997) and followed-up for the occurrence of IE (failure of > or = 2 drugs, > or = 1 seizure/month, over 18 months) [corrected]. Etiology and epilepsy syndromes were classified per International League Against Epilepsy guidelines. RESULTS: The median follow-up is 4.8 years, and 599 (97.7%) have been followed for more than 18 months. Sixty children (10.0%) have met the criteria for IE, including 34.6% with cryptogenic/symptomatic generalized, 2.7% with idiopathic, 10.7% with other localization-related, and 8.2% with unclassified epilepsy (p < 0.0001). After multivariable adjustment for epilepsy syndrome, initial seizure frequency (p < 0.0001), focal EEG slowing (p = 0.02), and acute symptomatic or neonatal status epilepticus (p = 0.001) were associated with an increased risk of IE, and age at onset between 5 and 9 years was associated with a lowered risk (p = 0.03). The absolute number of seizures and unprovoked or febrile status epilepticus were not associated substantially with IE. CONCLUSIONS: Approximately 10% of children meet criteria for IE early in the course of their epilepsy. Cryptogenic/symptomatic generalized syndromes carry the highest risk and idiopathic syndromes the lowest. Half of IE occurs in children with nonidiopathic localization-related syndromes. Initial seizure frequency is highly predictive of IE. By contrast, absolute number of seizures and unprovoked or febrile status epilepticus are not.

Age of Onset↗

PubMed1995

Regulation of Dictyostelium early development genes in signal transduction mutants.

The secreted cyclic nucleotide phosphodiesterase (PDE) and its glycoprotein inhibitor (PDI) are among the first genes expressed when Dictyostelium amoebae begin their development. We used a series of mutants with defects in signal transduction to ask whether cAMP receptors 1 and 3, G alpha2, G beta, adenylyl cyclase (ACA), or the protein kinase A catalytic subunit (PKAcat) are required for the initial appearance or later regulation of the PDE and the PDI transcripts. The PDE gene produces a 1.9-kb transcript during vegetative growth and then a 2.4-kb transcript during the early hours of development. Regulation of the 2.4-kb transcript in CAR1, G alpha2, G beta, and ACA mutants is similar to that of isogenic parental strains, although its level is reduced in strains that carry the CAR1 mutation. CAR1/CAR3 double mutants also produce less PDE transcript, but the PDE gene remains inducible by cAMP. The PKAcat mutant produces the 2.4-kb PDE transcript, but in this mutant the vegetative transcript is retained in development. CAR1 and CAR3 are not required for transcription of the PDI gene, but deleting CAR1 leads to overproduction of the PDI transcript. Induction or repression of the PDI gene does not require G alpha2, G beta, or ACA. PKAcat is required for synthesis of the PDI transcript. The results suggest a two-stage regulation of these early genes through a G alpha2/G beta-independent mechanism and an absolute dependence of PDI on the PKAcat.

Adenylyl Cyclases↗

PubMed2001

DBHR, a gene with homology to dopamine beta-hydroxylase, is expressed in the neural crest throughout early development.

In a screen for genes involved in neural crest development, we identified DBHR (DBH-Related), a putative monooxygenase with low homology to dopamine beta-hydroxylase (DBH). Here, we describe novel expression patterns for DBHR in the developing embryo and particularly the neural crest. DBHR is an early marker for prospective neural crest, with earliest expression at the neural plate border where neural crest is induced. Furthermore, DBHR expression persists in migrating neural crest and in many, though not all, crest derivatives. DBHR is also expressed in the myotome, from the earliest stages of its formation, and in distinct regions of the neural tube, including even-numbered rhombomeres of the hindbrain. In order to investigate the signals that regulate its segmented pattern in the hindbrain, we microsurgically rotated the rostrocaudal positions of rhombomeres 3/4. Despite their ectopic position, both rhombomeres continued to express DBHR at the level appropriate for their original location, indicating that DBHR is regulated autonomously within rhombomeres. We conclude that DBHR is a divergent member of a growing family of DBH-related genes; thus, DBHR represents a completely new type of neural crest marker, expressed throughout the development of the neural crest, with possible functions in cell-cell signaling.

Amino Acid Sequence↗

PubMed2005

NO as a mediator during the early development of the cardiovascular system in the zebrafish.

As a general pattern innervation of the cardiovascular system appears late during development in vertebrate embryos, and cardiovascular control may be achieved by hormonal activity in early stages. However, very little is known about the onset of NO-responsiveness during development, which in adult vertebrates is known to play a key function in many physiological processes such as control of vascular tone, neurotransmission, macrophage activity, and angiogenesis. Analysis of the effect of NO on the cardiovascular system in zebrafish (Danio rerio) embryos and larvae revealed almost no effect on cardiac activity during chronic exposure to NO-producing chemicals, whereas vascular reactivity was observed in veins and arteries of the zebrafish in early developmental stages (5-6 days post fertilization). Chronic exposure also modified the development of the vascular system. The presence of an NO donor (sodium nitroprusside) did not change the patterning of the vascular bed, but it induced an earlier appearance of some blood vessels in the trunk region of the zebrafish larvae. The data reveal that NO plays an important role in the development of the cardiovascular system and in the ontogeny of the cardiovascular control system in fish.

Animals↗

PubMed1980

The early development of corticobulbar and corticospinal systems. Studies using the North American opossum.

The North American opossum is born 12 days after conception and is therefore available for experimental manipulation in an immature state. We have used the opossum to study the growth of cortical axons into the brainstem and spinal cord and have obtained evidence that such growth occurs in an orderly fashion. Cortical axons reach the ventral mesencephalon 12 days after birth and some of them have grown into the caudal medulla where they decussate by 23 days. At the latter stage immature cortical axons also distribute to the midbrain tegmentum, the basilar pons, the inferior olive and the hilum of the nucleus cuneatus. Cortical axons first enter the spinal cord about 30 days after birth where they are present in the white matter before growing into the dorsal horn. The forelimb placing reaction does not develop until well after cortical axons have reached cervical levels. Axons from the cerebral cortex grow into the spinal cord before there is evidence for cortical innervation of either the red nucleus or the bulbar reticular formation and well before pyramidal cells of the neocortex are mature. The relatively late development of corticospinal and corticobulbar systems contrasts markedly with the early growth of bulbospinal axons.

Animals↗

PubMed1996

A comparison of the early development of ischemic brain damage in normoglycemic and hyperglycemic rats using magnetic resonance imaging.

The early evolution of ischemic brain injury under normoglycemic and streptozotocin-induced hyperglycemic plasma conditions was studied using magnetic resonance imaging (MRI). Male Sprague-Dawley rats were subjected to either permanent middle cerebral artery occlusion (MCAO), or 1-h MCAO followed by reperfusion using the intraluminal suture insertion method. The animals were divided into four groups each with eight rats: normoglycemia with permanent MCAO, normoglycemia with 1-h MCAO, hyperglycemia with permanent MCAO, and hyperglycemia with 1-h MCAO. Diffusion-weighted images (DWIs) and T2-weighted images (T2WIs) were aquired every 1 h from 20 min until 6 h after MCAO, at which time cerebral plasma volume images (PVIs) were acquired. Tissue infarction was determined by triphenyltetrazolium chloride staining at 7 h after MCAO. The ischemic damage, measured as the area of DWI and T2WI hyperintensity and tissue infarction, increased significantly in hyperglycemic rats in both permanent and transient MCAO models. In the permanent MCAO model, the maximal apparent water diffusion coefficient (ADC) decline under either normo- or hyperglycemia was about 40%, but the speed of ADC drop was faster in hyperlgycemic rats than in normoglycemic rats. Reperfusion after 1 h of MCAO in normoglycemic rats partly reversed the decline in ADC, whereas the low ADC area continued to expand after reperfusion in the hyperglycemic group. Between the two hyperglycemic groups with either permanent MCAO or reperfusion, no significant difference was found in the infarct volume measured at 7 h after MCAO. However, reperfusion dramatically increased the extent and accelerated the development rate of vasogenic edema. ADC in the hyperglycemic reperfusion group also dropped to a lower level. A large "no-reflow" zone was found in the ischemic hemisphere in the hyperglycemic reperfusion group. This study provides strong evidence to support that preischemic hyperglycemia exacerbates ischemic damage in both transient and permanent MCAO models and demonstrates, using MRI, that reperfusion under preischemic hyperglycemia accelerates the evolution of early ischemic injury.

Animals↗

PubMed2002

Early development of cancer chemoprevention clinical trials: studies of dietary calcium as a chemopreventive agent for human subjects.

Early cancer chemoprevention clinical trials in human subjects had to be carried out with large numbers of subjects studied for long durations, measuring cancer as an end point. However new findings on abnormal epithelial cell growth and development during the multistage evolution of colonic tumors made it possible to carry out chemoprevention clinical trials in several stages, with fewer subjects studied for shorter durations, thus enabling investigators to analyze increasing numbers of chemopreventive agents and nutritional regimens in clinical trials. Supplemental dietary calcium was the first candidate chemopreventive agent studied in this multistage approach in human subjects, as a putative agent for colon cancer prevention. Early- and late-stage intermediate biomarker studies in humans have strongly suggested utility for supplemental dietary calcium to inhibit the development of benign and subsequent malignant colonic neoplasms. Preclinical experimental studies have further demonstrated the ability of increased dietary calcium to inhibit the evolution of colonic tumors when they were induced by targeted mutations, dietary factors, and particularly when given over a long duration of lifespan.

Anticarcinogenic Agents↗

PubMed1986

Specificity of neuromuscular connections during early development and following regeneration of motor axons in the bullfrog.

The specificity of neuromuscular connectivity was examined in unoperated bullfrog (Rana catesbeiana) tadpoles and in tadpoles that had undergone transection of the three ventral roots that normally innervate the hindlimb. The specificity of motoneuron projections was assessed by applying small amounts of horseradish peroxidase to circumcribed hindlimb regions and mapping the locations of retrogradely labeled motoneurons within the lumbar lateral motor column (LMC). In unoperated tadpoles, the locations of retrogradely labeled motoneurons in the LMC were as circumscribed at early stages of development as in tadpoles examined after motoneuron number in the LMC had stabilized. Six to eight weeks after ventral root transection in young tadpoles, localization of retrogradely labeled motoneurons was almost as circumscribed as found in unoperated tadpoles. However, localization following regeneration became less precise in more advanced tadpoles. If the ventral roots of adult frogs were crushed rather than transected, motor axon regeneration was considerably more precise, confirming previous reports (Westerfield and Powell, 1983). The implications of these results for hypotheses of neuromuscular specificity are discussed.

Animals↗

PubMed2001

Seed development: Early paternal gene activity in Arabidopsis.

Both parental genomes are expressed during embryogenesis, although the time of activation of the paternally inherited genes varies between organisms. Results reported by Vielle-Calzada et al. have suggested that delayed activation of the paternal genome seems to be the rule in plant development. We find, however, that during early embryogenesis in Arabidopsis, paternal genes are expressed and are sufficient for normal development. Our findings indicate that there is no overall maternal control of early embryogenesis, and that the contribution of the parental alleles needs to be assessed for each gene individually.

Arabidopsis↗

PubMed2001

3,4-methylenedioxymethamphetamine (ecstasy)-induced learning and memory impairments depend on the age of exposure during early development.

Use of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has increased dramatically in recent years, yet little is known about its effects on the developing brain. Neonatal rats were administered MDMA on days 1-10 or 11-20 (analogous to early and late human third trimester brain development). MDMA exposure had no effect on survival but did affect body weight gain during treatment. After treatment, body weight largely recovered to 90-95% of controls. MDMA exposure on days 11-20 resulted in dose-related impairments of sequential learning and spatial learning and memory, whereas neonatal rats exposed on days 1-10 showed almost no effects. At neither stage of exposure did MDMA-treated offspring show effects on swimming ability or cued learning. Brain region-specific dopamine, serotonin, and norepinephrine changes were small and were not correlated to learning changes. These findings suggest that MDMA may pose a previously unrecognized risk to the developing brain by inducing long-term deleterious effects on learning and memory.

3,4-Methylenedioxyamphetamine↗

PubMed1975

Inhibition of RNA synthesis by acetyl salicylate and actinomycin D during early development in the mouse.

Experiments were designed to ascertain and compare the effects of acetyl salicylate and actinomycin D on RNA synthesis in mouse oocytes in vitro and in vivo. After exposure to the drugs the effects on RNA synthesis were measured by incorporation of [3H]uridine and autoradiography. The results indicate that acetyl salicylate inhibits RNA synthesis in the treated oocytes as does actinomycin D. The only difference in the effects of these two drugs is that salicylate inhibits RNA synthesis to a much lesser degree than does actinomycin D. Effects from a short exposure to salicylate may be reversible; the same effects with actinomycin D cannot be reversed. In utero exposure of the female fetus may lead to partial or total sterility (depending on the dose and time of exposure) of that fetus and/or abnormal development of the progeny from those mice (F2). These results suggest that RNA synthesis in early oogenesis is a vital part of later development of the oocytes in adult mouse ovary. Inhibition of RNA may be one of the causes of malformations and sterility.

Animals↗

PubMed1995

DNA methylation in early development.

Several lines of evidence strongly suggest that DNA methylation is involved in embryo development. Perhaps the most direct evidence comes from experiments with methyltransferase deficient mice. Embryos that express low levels of the maintenance methyltransferase do not develop to term and die at the 5 to 20 somite stage corresponding to the level of the enzyme. In the mouse, dramatic methylation changes have been observed during the early steps of embryo development. Most genes are subject to a process of active demethylation starting promptly after fertilization. Except for a small number of methylated CpG sites in imprinted genes the vast majority of the sites are unmethylated by the stage of cavitation (16 cell). Such genome-wide demethylation may signify an erasure of epigenetic information originating in the highly differentiated gametes. This erasure may be essential for the establishment of a pluripotent state, before specific cell lineages can be determined. The process of laying down a new developmental program involves, initially, global de novo methylation at the stage of pregastrulation followed by gene specific demethylations associated with the onset of activity of these genes. CpG islands characteristic of housekeeping genes, appear to be protected from the global de novo methylation. An exception to this rule is the hypermethylation of CpG islands in X-linked housekeeping genes on the inactive X chromosome and of specific differentially methylated CpG sites in imprinted genes. Primordial germ cells escape the global de novo methylation which takes place at the pregastrula stage and undergo a very similar de novo methylation process in the differentiated gonads (15.5-18.5 days post coitum), forming the methylation patterns which are specific to the gametes. Specific demethylations then form a terminal methylation pattern which is then clonaly inherited in the soma and erased after fertilization.

Animals↗

PubMed2002

Ultrastructural study of the early development and localization of Loma salmonae in the gills of experimentally infected rainbow trout.

The early ultrastructural stages of Loma salmonae were studied in the gills of experimentally infected rainbow trout. No parasitic stages were identified during the first 2 wk of the infection. By week 3 postexposure (PE), uninucleate and binucleate meronts were recognized within host cells (no xenomas) associated with the capillary channels of secondary lamellae and lamellar arteries. An inflammatory reaction was absent. In secondary lamellae, infected cells were isolated from the capillary lumen, and some were recognized as pillar cells. In lamellar arteries, infected cells were localized beneath the endothelium and not in the lumen. Inflammatory reaction and destruction of parasites inside blood cells in the lumen of secondary lamellae were observed by week 4 PE. Three hypotheses, i.e., isolation, internalization, and evasion, are proposed to explain the localization of the infected cells in the gills. It is concluded that meronts are the earliest parasitic stage observed by week 3 PE, pillar cells are secondarily infected by phagocytosis of infected cells in the blood, endothelial cells of gills are not infected, and inflammatory response to the parasite starts by week 4 PE.

Animals↗

PubMed1999

Expression of the hexose transporters GLUT1 and GLUT2 during the early development of the human brain.

We used immunohistochemistry with anti-glucose transporter antibodies to document the presence of facilitative hexose transporters in the fetal human brain. GLUT1 is expressed in all regions of the fetal brain from ages 10 to 21 weeks. GLUT1 was present in the endothelial cells of the brain capillaries, the epithelial cells of the choroid plexus and neurons. High expression of GLUT2 was observed in the granular layer of the cerebellum in brains 21 weeks old, but GLUT2 immunoreactivity was absent at earlier stages. GLUT3 and GLUT4 immunoreactivities were absent at all stages studied. GLUT5 immunoreactivity was evident only in the cerebellar region of 21-week old fetal brains. We conclude that GLUT1 plays a fundamental role in early human brain development. The data also suggest that the cerebellum of the developing brain has the capacity to transport fructose, a substrate that has not been previously identified as a source of metabolic energy in the adult human brain.

Brain↗

PubMed1983

Early development of selenium-induced cataract: slit lamp evaluation.

The purpose of our research was to document early lenticular changes preceding cataract formation in rats receiving an elevated dose of selenium. The following stages were observed after selenium injection: Stage 1 (13-24 hr post-injection), formation of posterior equatorial subcapsular cataract (PESC); Stage 2 (24-72 hr), decline of the PESC, development of a prominent 'washer' shaped change in the refraction of the cortex, and first appearance of swollen fibers around the nucleus; Stage 3 (three to five days), appearance of bilateral dense central nuclear cataracts and further development of perinuclear swollen fibers; Stage 4 (five to 10 days), some nuclear cataracts became more opaque and/or angular. The results are consistent with the hypothesis that the initial site of action of selenium in nuclear cataract formation is not in the lens nucleus. Rather, selenium causes early changes outside the nucleus, which are followed by nuclear cataracts.

Animals↗