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R Schnabel

Publications and source records attributed to R Schnabel.

At least 55 records · Page 3Linked to original sources

Complexity of developmental control: analysis of embryonic cell lineage specification in Caenorhabditis elegans using pes-1 as an early marker.

In the early Caenorhabditis elegans embryo five somatic founder cells are born during the first cleavages. The first of these founder cells, named AB, gives rise to 389 of the 558 nuclei present in the hatching larva. Very few genes directly involved in the specification of the AB lineage have been identified so far. Here we describe a screen of a large collection of maternal-effect embryonic lethal mutations for their effect on the early expression of a pes-1::lacZ fusion gene. This fusion gene is expressed in a characteristic pattern in 14 of the 32 AB descendants present shortly after the initiation of gastrulation. Of the 37 mutations in 36 genes suspected to be required specifically during development, 12 alter the expression of the pes-1::lacZ marker construct. The gene expression pattern alterations are of four types: reduction of expression, variable expression, ectopic expression in addition to the normal pattern, and reduction of the normal pattern together with ectopic expression. We estimate that approximately 100 maternal functions are required to establish the pes-1 expression pattern in the early embryo.

Animals↗

Anterior organization of the Caenorhabditis elegans embryo by the labial-like Hox gene ceh-13.

The Caenorhabditis elegans lin-39, mab-5 and egl-5 Hox genes specify cell fates along the anterior-posterior body axis of the nematode during postembryonic development, but little is known about Hox gene functions during embryogenesis. Here, we show that the C. elegans labial-like gene ceh-13 is expressed in cells of many different tissues and lineages and that the rostral boundary of its expression domain is anterior to those of the other Hox genes. By transposon-mediated mutagenesis, we isolated a zygotic recessive ceh-13 loss-of-function allele, sw1, that exhibits an embryonic sublethal phenotype. Lineage analyses and immunostainings revealed defects in the organization of the anterior lateral epidermis and anterior body wall muscle cells. The epidermal and mesodermal identity of these cells, however, is correctly specified. ceh-13(sw1) mutant embryos also show fusion and adhesion defects in ectodermal cells. This suggests that ceh-13 plays a role in the anterior organization of the C. elegans embryo and is involved in the regulation of cell affinities.

Amino Acid Sequence↗

The nitric oxide donor sodium nitroprusside is protective in ischemia/reperfusion injury of the pancreas.

BACKGROUND: The role of nitric oxide in the ischemia/reperfusion injury of the pancreas is still unclear. In other organs, protective as well as aggravating effects have been described. We have, therefore, investigated the effect of the nitric oxide donor sodium nitroprusside on pancreatic ischemia/reperfusion injury. METHODS: In Landrace pigs, after transsection of the pancreas, complete vascular isolation of the pancreatic tail was performed. The tail was subjected to 3 hr of warm ischemia and thereafter reperfusion (6 hr). The animals were divided into a control group (n=7) and a treatment group (n=7) that received 15 mg of sodium nitroprusside after reperfusion intra-arterially into the splenic artery. RESULTS: The morphological tissue damage and lipase activity in the venous effluent of the pancreas were significantly lower in the treatment group. Partial oxygen tension in the tissue after reperfusion was markedly reduced in the control group, indicating an impairment of microcirculation. In the treatment group, however, partial oxygen tension in the tissue was significantly higher (43 vs. 20 mmHg; P<0.014). Furthermore, total blood flow through the pancreatic tail in the treatment group was found to be significantly higher in the late reperfusion period (14 vs. 9.5 ml/min at 5 hr after reperfusion; P<0.05). CONCLUSION: There is a marked impairment of pancreatic microcirculation after reperfusion. Sodium nitroprusside counteracts this impairment and has a protective effect on ischemia/reperfusion injury of the pancreas.

Adenosine Triphosphate↗

cyk-1: a C. elegans FH gene required for a late step in embryonic cytokinesis.

A maternally expressed Caenorhabditis elegans gene called cyk-1 is required for polar body extrusion during meiosis and for a late step in cytokinesis during embryonic mitosis. Other microfilament- and microtubule-dependent processes appear normal in cyk-1 mutant embryos, indicating that cyk-1 regulates a specific subset of cytoskeletal functions. Because cytokinesis initiates normally and cleavage furrows ingress extensively in cyk-1 mutant embryos, we propose that the wild-type cyk-1 gene is required for a late step in cytokinesis. Cleavage furrows regress after completion of mitosis in cyk-1 mutants, leaving multiple nuclei in a single cell. Positional cloning and sequence analysis of the cyk-1 gene reveal that it encodes an FH protein, a newly defined family of proteins that appear to interact with the cytoskeleton during cytokinesis and in the regulation of cell polarity. Consistent with cyk-1 function being required for a late step in embryonic cytokinesis, we show that the CYK-1 protein co-localizes with actin microfilaments as a ring at the leading edge of the cleavage furrow, but only after extensive furrow ingression. We discuss our findings in the context of other studies suggesting that FH genes in yeast and insects function early in cytokinesis to assemble a cleavage furrow.

Actin Cytoskeleton↗

Vasopressin administration modulates anxiety-related behavior in rats.

Experiments were performed to measure the influence of centrally and peripherally applied arginine vasopressin (AVP) on anxiety-related behavior as indicated by the elevated plus maze test. Central administration was performed into the septum using a microdialysis technique. In initial experiments, the microdialysis probes were characterized for substance application in vivo by means of 125I AVP, measuring the substance-specific percent passover and the spatial distribution around the microdialysis membrane within the brain. Both microdialysis administration of 200 pg of AVP into the septum and and intraperitoneal application of 500 ng of AVP induced an increase in the percentage of time spent on the open arms of the elevated plus maze. The blockade of vasopressinergic neurotransmission or neuromodulation into the septal area by 40 ng of the AVP receptor antagonist d(CH2)5Thyr(Et)VAVP failed to induce a significant effect in this respect. The observation that neither centrally nor peripherally applied AVP influenced the locomotor activity on the elevated plus maze supports the hypothesis that AVP is involved in the modulation of anxiety-related behavior in rats.

Animals↗

Serine hydroxymethyltransferase is maternally essential in Caenorhabditis elegans.

The mel-32 gene in the free living soil nematode Caenorhabditis elegans encodes a serine hydroxymethyltransferase (SHMT) isoform. Seventeen ethylmethanesulfonate (EMS)-induced mutant alleles of mel-32(SHMT) have been generated, each of which causes a recessive maternal effect lethal phenotype. Animals homozygous for the SHMT mutations have no observable mutant phenotype, but their offspring display an embryonic lethal phenotype. The Mel-32 phenotype has been rescued with a transgenic array containing only mel-32(SHMT) genomic DNA. Heteroduplex analysis of the 17 alleles allowed 14 of the mutations to be positioned to small regions. Subsequent sequence analysis has shown that 16 of the alleles alter highly conserved amino acids, while one allele introduces a stop codon that truncates two thirds of the predicted protein. mel-32(SHMT) has a 55-60% identity at the amino acid level with both isoforms of SHMT found in yeast and humans and a 50% identity with the Escherichia coli isoform. The C. elegans mel-32 mutation represents the first case where SHMT has been shown to be an essential gene.

Amino Acid Sequence↗

Ischemia/reperfusion injury of the pancreas: a new animal model.

BACKGROUND: Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process. MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion. RESULTS: A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment. CONCLUSION: These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas.

Adenine Nucleotides↗

Buccal capsule development as a consideration for phylogenetic analysis of Rhabditida (Nemata).

Bacterial feeding nematodes in the order Rhabditida including Zeldia punctata (Cephalobidae) and Caenorhabditis elegans (Rhabditidae) differ profoundly in the buccal capsule parts and associated cells. We carried out a range of tests to determine which buccal capsule parts and cells are evolutionarily homologous between the representative species of the two families. Tests included reconstruction of the buccal capsule and procorpus with transmission electron microscopy (TEM), nuclei position and morphology using 4, 6-diamidino-2-phenylindole (DAPI) staining, and cell lineage using four dimensional (4D) microscopy. The lining of the buccal capsule of Z. punctata and additional Cephalobidae includes four sets of muscular radial cells, ma, mb, mc and md, in contrast to C. elegans and additional Rhabditidae, which has two sets of epithelial cells (e1, e3) and two sets of muscle cells (m1, m2). Cell lineage of a nematode closely related to Z. punctata, Cephalobus cubaensis, supports the hypothesis that in cephalobids the e1 and e3 cells become hypodermal cells or are programmed to die. Our findings contradict all previous hypotheses of buccal capsule homology, and suggest instead that ma and mb in Z. punctata are homologous to m1 and m2 in C. elegans respectively. We also hypothesize that ma and mb could be homologous to primary and secondary sets of stylet-protractor muscle cells in the plant parasitic Tylenchida.

Animals↗

[XY gonadal dysgenesis (Swyer syndrome) with gonadoblastoma].

This is a case report of 46 xy gonadal dysgenesis (Swyer-syndrome) with bilateral androgen producing gonadoblastoma in streak gonads in a 15-year-old patient. The presenting features were: hypergonadotrophic hypogonadism, male pseudohermaphroditism and virilisation. A hypoplastic uterus with normal looking Fallopian tubes and bilateral adnexal tumors were detected through laparoscopy. A laparotomy was performed and the streak gonads with bilateral gonadoblastoma were removed. This led to a normalisation of serum testosterone and serum beta-HCG levels and an amelioration of signs of virilisation. Uterus and fallopian tubes were conserved during the operation. A second look laparoscopy 6 months later showed no evidence of recurrent tumor. No mutation were found in the sex-determining gene (SRY) on DNA-screening using SSCP assay.

Adolescent↗

Binary specification of the embryonic lineage in Caenorhabditis elegans.

In Caenorhabditis elegans, the early embryo contains five somatic founder cells (known as AB, MS, E, C and D) which give rise to very different lineages. Two simply produce twenty intestinal (E) or muscle (D) cells each, whereas the remainder produce a total of 518 cells which collectively contribute in a complex pattern to a variety of tissues. A central problem in embryonic development is to understand how the developmental potential of blastomeres is restricted to permit the terminal expression of such complex differentiation patterns. Here we identify a gene, lit-1, that appears to play a central role in controlling the asymmetry of cell division during embryogenesis in C. elegans. Mutants in lit-1 suggest that its product controls up to six consecutive binary switches which cause one of the two equivalent cells produced at each cleavage to assume a posterior fate. Most blastomere identities in C. elegans may therefore stem from a process of stepwise binary diversification.

Animals↗

Localization of dopamine D1 receptors and dopaminoceptive neurons in the chick forebrain.

The distributions of dopamine D1 receptors, dopaminoceptive neurons, and catecholaminergic fibers were investigated in the forebrain of the domestic chick by using D1 receptor autoradiography and immunohistochemical detection of D1 receptor protein (D1rp), the dopamine- and cAMP-regulated phosphoprotein DARPP-32, and tyrosine hydroxylase (TH). Particular attention was paid to two forebrain regions, the mediorostral neostriatum/ hyperstriatum ventrale (MNH) and neostriatum dorsocaudale (Ndc), which have been shown to be crucially involved in filial imprinting. In general, there was a good, but not complete, correlation between the immunohistochemical pattern of DARPP-32 positive perikarya and the distribution of D1 receptors. Both, DARPP-32 positive neurons as well as D1 receptors were highly enriched in the striatal part of the basal ganglia including the lobus parolfactorius (LPO) and paleostriatum augmentatum. High to moderate densities were observed in the outer rind of the pallium. Low to moderate densities were found in the belt regions of primary sensory areas, whereas densities in the respective core regions were generally low. Labeling in the MNH and Ndc was heterogeneous. Whereas the neostriatal part of MNH displayed both, moderate DARPP-32 immunostaining and moderate D1 receptor densities, the hyperstriatal part showed also moderate D1 receptor densities but was only weakly labeled by DARPP-32. The rostral part of the Ndc was among the most intensely DARPP-32 labeled areas of the pallium, its caudal part revealed only moderate DARPP-32 immunostaining. By using D1 receptor autoradiography, a homogeneous labeling throughout the rostrocaudal extension of the Ndc was found. Double-labeling experiments with antibodies to DARPP-32 and TH revealed that TH positive fibers in the MNH, Ndc, and LPO were often closely related to DARPP-32 positive perikarya. At the ultrastructural level, both immunoreaction for D1rp and DARPP-32 in the MNH and Ndc were primarily found to be associated with postsynaptic elements. Whereas D1rp immunoreactivity was enriched at postsynaptic densities or in their vicinity, reaction product for DARPP-32 was present throughout the perikaryal cytoplasm, dendrites, and dendritic spines. These results indicate that DARPP-32 as well as D1 receptors in the avian forebrain reveal a distribution that is substantially similar to that of mammals.

Animals↗

Assessing normal embryogenesis in Caenorhabditis elegans using a 4D microscope: variability of development and regional specification.

Caenorhabditis elegans is renowned for its invariant embryogenesis. This pattern of development is in apparent contrast to other organisms from Drosophila to higher vertebrates. With the aid of a 4D microscope system (multifocal, time-lapse video recording system) which permits the extensive documentation and analysis of cell divisions, cell positions, and migrations in single embryos we have analyzed normal embryogenesis of C. elegans. The instrumentation reveals a naturally occurring variability in cell division timing, cell positioning, and cell-cell contacts which could not have been detected by the direct observation used earlier (Sulston et al., 1983, Dev. Biol. 100, 64-119). Embryos are very flexible and produce an essentially invariant premorphogenetic stage from variable earlier stages. An analysis of the distribution of the descendants of the early founder blastomeres at the premorphogenetic stage shows that these establish discrete regions in the embryo, a process involving a considerable amount of cell movement, which again varies in different embryos. Only cell fate assignment remains invariant. However, as shown earlier, this is not due to an autonomous invariant specification of cell fates but due to the fact that cell-cell interactions occur very early when the topology of blastomeres in the embryo is still sufficiently precise to ensure reproducible patterns of inductions. A new concept that founder blastomeres produce embryonic regions in the embryo can explain the striking complexity of the lineage per se and also the complicated asymmetric lineage patterns by which the bilateral symmetry of the embryo is established. Many cells, including bilateral homologs, were apparently chosen for a specific fate solely by their position in the embryo, irrespectively of the lineage descent by which the cells are created. We postulate that the production of regions by cell-cell interactions is the pivotal principle guiding the embryogenesis of C. elegans and that the embryogenesis of the worm follows the same basic principles as embryogenesis in other organisms.

Animals↗

Why does a nematode have an invariant cell lineage?

C. elegans is renowned for its invariant embryogenesis and functions as a major paradigm for a mode of development coupled to an invariant lineage. Recent work, however, suggests that the embryogenesis of the nematode is much more flexible than anticipated. The invariant premorphogenetic stage is formed from variable earlier stages through a sorting of cells. Cells do not act as individuals but already early in embryogenesis a regionalization of the embryo occurs. Cells are diversified by a binary specification of 'abstract' blastomere (regional) identities. The determination of tissues may thus be a very late event. It appears that C. elegans, although assigning cell fates in an invariant lineage pattern, uses the same strategies and mechanisms for embryogenesis as organisms with variable lineages.

Journal Article↗

Role of the dorso-caudal neostriatum in filial imprinting of the domestic chick: a pharmacological and autoradiographical approach focused on the involvement of NMDA-receptors.

Newly hatched domestic chicks were either acoustically imprinted on 400 Hz tone pulses or visually imprinted on a rotating red light. Compared to naive control animals, both groups of imprinted chicks expressed significantly enhanced stimulus evoked 2-fluoro-2-deoxyglucose (2-FDG) uptake in circumscribed areas of the dorso-caudal neostriatum (Ndc). This enhanced excitability after imprinting seems not to be related to changes of NMDA-receptor densities as measured by quantitative receptor autoradiography. However, pharmacological blockade of NMDA-receptors in the dorso-caudal neostriatum leads to a marked suppression of stimulus-evoked 2-FDG uptake in the dorso-caudal neostriatum and also in the interconnected imprinting relevant forebrain area, medio-rostral neostriatum/hyperstriatum ventrale (MNH). Furthermore, chicks which received bilateral Ndc injections of the competitive NMDA antagonist DL-2-amino-5-phosphono valeric acid (APV) during the imprinting experiments showed a dose-dependent decrease of imprinting success compared to vehicle-injected controls. These results indicate that the dorso-caudal neostriatum may represent a polysensory associative brain region in which visual and acoustic features of imprinting objects may be integrated. The activation in this area evoked by the imprinting stimulus during and after imprinting is critically dependent on NMDA-receptor activation, which appears to be required for this learning process.

2-Amino-5-phosphonovalerate↗

Lack of influence of histopathological changes on carbamazepine and carbamazepine-10, 11-epoxide concentrations in the brain cortex of epileptic patients.

Post-mortem concentrations of carbamazepine (CBZ) and its anticonvulsive metabolite carbamazepine-10,11-epoxide (CE) were determined in different lesions of the cerebral cortex and in the serum (total and free) from 13 epileptic patients. Twenty cortical specimens were obtained from the superior frontal gyrus, the temporopolar region and the neocerebellum. The cortical samples showed various pathological changes characterized by augmented glial cells, fibre gliosis or ulegyria as well as abundant corpora amylacea or encephalitic signs of viral type besides neuronal depletion. The CBZ and CE concentrations in the 20 cortical lesions were not significantly decreased when compared to the control specimens of 32 epileptic patients without essential histopathological alterations of the specified cortical areas (p < 0.05). A comparable result had been found in our former study on phenytoin (PHT) and phenobarbital (PB). Six patients with cortical lesions of the present series had already been included in this PHT/PB study. Five of these patients revealed unchanged CBZ and CE as well as PHT and PB concentrations. Only in one neocerebellar specimen the CE concentration was just above the upper 95% confidence limit of the control group. But, most probably this finding has no further relevance. The results greatly favour the nonspecific binding of CBZ and CE to cerebral tissue constituents.

Adult↗

Development of dopamine receptors in the forebrain of the domestic chick in relation to auditory imprinting. An autoradiographic study.

The rostro-medial neostriatum/hyperstriatum ventrale (MNH) and the neostriatum dorsocaudale (Ndc) are forebrain regions which play a role in auditory filial imprinting. Both regions receive a distinct dopaminergic input from the mesencephalon and we were interested to investigate if the dopaminergic system, which is known to play a role in associative learning processes and neuronal plasticity is involved in auditory imprinting. Using ligand autoradiography we studied the distribution and density of dopamine receptors (D1 and D2 type) in the forebrain of socially isolated chicks during the first postnatal week and compared these data with the values of age-matched imprinted chicks. D1- and D2-receptors were present in the chick forebrain on the day of hatching and they showed in general, the same distribution until postnatal day 7. Between days 0 and 2 the D2-receptor density increased significantly in the lobus parolfactorius and paleostriatum augmentatum while for D1-receptor density no significant changes were detectable. The receptor densities in the investigated forebrain regions did not differ significantly between imprinted and control chicks. These results suggest that auditory imprinting does not induce alterations of dopamine receptor density, however, more subtle changes can not be excluded. The presented detailed data about the developmental profile of dopamine receptors within distinct brain regions is a further step towards a more specific interpretation of behavioral effects of dopamine receptor agonists or antagonists at different postnatal ages.

Acoustic Stimulation↗