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Biomedical subjects

Dirk Meyer

Publications and source records attributed to Dirk Meyer.

17 recordsLinked to original sources
PubMed2005

Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations.

Synapse formation requires the coordination of pre- and postsynaptic differentiation. An unresolved question is which steps in the process require interactions between pre- and postsynaptic cells, and which proceed cell-autonomously. One current model is that factors released from presynaptic axons organize postsynaptic differentiation directly beneath the nerve terminal. Here, we used neuromuscular junctions (NMJs) of the zebrafish primary motor system to test this model. Clusters of neurotransmitter (acetylcholine) receptors (AChRs) formed in the central region of the myotome, destined to be synapse-rich, before axons extended and even when axon extension was prevented. Time-lapse imaging revealed that pre-existing clusters on early-born slow (adaxial) muscle fibers were incorporated into NMJs as axons advanced. Axons were, however, required for the subsequent remodeling and selective stabilization of synaptic clusters that precisely appose post- to presynaptic elements. Thus, motor axons are dispensable for the initial stages of postsynaptic differentiation but are required for later stages. Moreover, many AChR clusters on later-born fast muscle fibers formed at sites that had already been contacted by axons, suggesting heterogeneity in the signaling mechanisms leading to synapse formation by a single axon.

Animals↗
PubMed2005

Evaluation of analytical methods and workflow performance of the Architect ci8200 integrated serum/plasma analyzer system.

BACKGROUND: The Architect ci8200 is an integrated serum analyzer for photometric, electrochemical and immunological assays. Several assays of each category and the workflow performance of the system were compared with established laboratory procedures in two laboratories. METHODS: Measurements were compared with the ELECSYS 2010 (Roche Diagnostics) for CEA, PSA, FPSA, AFP, folate, vitamin B12, with the CENTAUR (Bayer) for TSH, T4, FT4, FSH and Estradiol, with the LIAISON (DiaSorin) for TSH, FT4 and FT3, with the Behring Nephelometer BN II (Dade-Behring) for ferritin, and with the INTEGRA 800 (Roche Diagnostics), and the AU640 (Olympus) for clinical chemistry assays. Workflow studies were performed to compare times of analysis required for defined analytical workloads. RESULTS: The coefficients of variation (CVs) for within-run imprecision were between 3% and 6% for CEA, PSA, FPSA, AFP and ferritin, and between 3% and 11% for TSH, FT4, FT3, folate and vitamin B12. The CVs for day-to-day imprecision for immunoassays were between 3% and 10%, except for vitamin B12 (CVs 11-13%) and FT4 (CV 10% -13%). For clinical chemistry tests corresponding CVs for within-run imprecision were < 1%, except for HDL, triglyceride, creatinine, ALT, LD and lipase (CVs<2%) and bicarbonate (CV 3%-6%) and magnesium (CV < 3%). The CVs for day-to-day imprecision for clinical chemistry tests were < 1%, except for sodium, CO(2), magnesium, phosphorus, glucose, uric acid, HDL, triglyceride, ALT, AST CK, lipase with CVs < 6% and for CO(2)<11%. Dilutional linearity testing of seven immunoassays and five clinical chemistry analytes resulted in recovery rates of 90-110%. Correlation studies with 15 immunoassays and 25 clinical chemistry tests showed acceptable agreements with established methods. Work flow analyses demonstrated a net gain in time of analysis up to 109 min depending on the size of the sample batch analyzed with the Architect ci8200 as the main analyzer as compared to the currently installed routine laboratory equipment. Median turn-around times were 7 and 30 min for chemistry assays and immunoassays, respectively, when ordered as STAT analyses, and 18 min when chemistry assays were ordered as routine determinations. CONCLUSIONS: Assays on the Architect ci8200 performed well, fulfilling quality control requirements as defined for instance by German quality control guidelines (RiliBAK). Method comparisons showed acceptable agreements with established assays. Workflow studies using the Architect ci8200 documented shorter times of analyses as compared with the conventionally established laboratory routine demonstrating the potential of integrated chemistry/immunoassay analyzers to provide faster and more efficient performance.

Bicarbonates↗
PubMed2005

[Personal budget for persons in need of care. A socio-economic change with new perspectives for supply and demand].

In October 2004, in Germany a pre-operating study was started in order to prove the feasibility and consequences of the use of personal budgets by persons who are in need of nursing care. About 1000 care dependent persons living in seven regions are included in this triannual study. For three years they receive a budget amounting to 100 percent of their right of benefit in kind according to the German compulsory long-term care insurance. This budget has to be used exclusively for care-related services and must not be spent for assistance delivered by family members or neighbours. From socio-economic perspectives, the personal budget will result in a promotion of individuals instead of certain services or service institutions. An analysis shows, that the consequences might be an increased efficiency and effectiveness as well as structural changes within the supply of nursing care services. But to achieve these advantages, certain conditions must be provided. At first, the amount of the budget has to correspond to the individual need of care, which can change over time. Secondly, a misapplication of the personal fund has to be prevented without to exclude the potential of local or family dedication. And finally, new ways of quality assurance are requested due to the scope for development, which arises through deregulation.

Budgets↗
PubMed2004

Organization of cardiac chamber progenitors in the zebrafish blastula.

Organogenesis requires the specification of a variety of cell types and the organization of these cells into a particular three-dimensional configuration. The embryonic vertebrate heart is organized into two major chambers, the ventricle and atrium, each consisting of two tissue layers, the myocardium and endocardium. The cellular and molecular mechanisms responsible for the separation of ventricular and atrial lineages are not well understood. To test models of cardiac chamber specification, we generated a high-resolution fate map of cardiac chamber progenitors in the zebrafish embryo at 40% epiboly, a stage prior to the initiation of gastrulation. Our map reveals a distinct spatial organization of myocardial progenitors: ventricular myocardial progenitors are positioned closer to the margin and to the dorsal midline than are atrial myocardial progenitors. By contrast, ventricular and atrial endocardial progenitors are not spatially organized at this stage. The relative orientations of ventricular and atrial myocardial progenitors before and after gastrulation suggest orderly movements of these populations. Furthermore, the initial positions of myocardial progenitors at 40% epiboly indicate that signals residing at the embryonic margin could influence chamber fate assignment. Indeed, via fate mapping, we demonstrate that Nodal signaling promotes ventricular fate specification near the margin, thereby playing an important early role during myocardial patterning.

Animals↗
PubMed2004

Zebrafish mnx genes in endocrine and exocrine pancreas formation.

The pancreas consists of two components, which exert distinct homeostatic function, an endocrine part that secretes hormones including insulin and an exocrine part that produces digestive enzymes. In mouse, one of the factors essential for development of the pancreas is the Mnx-class homeobox transcription factor Hb9. Genetic studies showed that Hb9 is required for both initial morphogenesis of the pancreas as well as subsequent differentiation of insulin-producing beta-cells [Nat. Genet. 23 (1999) 71; Nat. Genet. 23 (1999) 67]. To get a better understanding of what role mnx genes play in pancreas development, we isolated and characterized mnx genes in the model organism zebrafish. We found one gene with homology to hb9 orthologs and two that display homology to the related chicken mnr2. Embryonic expression of the zebrafish mnx genes is very dynamic and is detected in derivatives of all three germ layers. Endodermal expression of hb9 takes place in the early gut endoderm and, later, in the endocrine pancreas and the swim bladder. In addition, one of the mnr2 genes, mnr2a, shows expression in an endodermal cell population that is initially intermingled with insulin-positive cells and that later becomes restricted to the exocrine pancreas. In knockdown studies using antisense morpholinos, we show that hb9 is essential for differentiation of the insulin-producing beta-cells but unlike mouse Hb9 is not needed for early morphogenesis of the pancreas. In contrast, mnr2a is required during late morphogenesis of the exocrine pancreas. In summary, our data suggest a tissue-specific mnx-expression code in the zebrafish pancreas and they reveal a novel role of an mnr2-related gene.

Air Sacs↗
PubMed2004

Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fates.

We have characterized and mapped the zebrafish ptf1a gene, analyzed its embryonic expression, and studied its role in pancreas development. In situ hybridization experiments show that from the 12-somite stage to 48 hpf, ptf1a is dynamically expressed in the spinal cord, hindbrain, cerebellum, retina, and pancreas of zebrafish embryos. Within the endoderm, ptf1a is initially expressed at 32 hpf in the ventral portion of the pdx1 expression domain; ptf1a is expressed in a subset of cells located on the left side of the embryo posteriorly to the liver primordium and anteriorly to the endocrine islet that arises from the posterodorsal pancreatic anlage. Then the ptf1a expression domain buds giving rise to the anteroventral pancreatic anlage that grows posteriorly to eventually engulf the endocrine islet. By 72 hpf, ptf1a continues to be expressed in the exocrine compartment derived from the anteroventral anlage. Morpholino-induced ptf1a loss of function suppresses the expression of the exocrine markers, while the endocrine markers in the islet are unaffected. In mind bomb (mib) mutants, in which delta-mediated notch signalling is defective [Dev. Cell 4 (2003) 67], ptf1a is normally expressed. In addition, the slow-muscle-omitted (smu) mutants that lack expression of endocrine markers because of a defective hedgehog signalling [Curr. Biol. 11(2001) 1358] exhibit normal levels of ptf1a. This indicates that hedgehog signaling plays a different genetic role in the specification of the anteroventral (mostly exocrine) and posterodorsal (endocrine) pancreatic anlagen.

Animals↗
PubMed2004

Prep1.1 has essential genetic functions in hindbrain development and cranial neural crest cell differentiation.

In this study we analysed the function of the Meinox gene prep1.1 during zebrafish development. Meinox proteins form heterotrimeric complexes with Hox and Pbx members, increasing the DNA binding specificity of Hox proteins in vitro and in vivo. However, a role for a specific Meinox protein in the regulation of Hox activity in vivo has not been demonstrated. In situ hybridization showed that prep1.1 is expressed maternally and ubiquitously up to 24 hours post-fertilization (hpf), and restricted to the head from 48 hpf onwards. Morpholino-induced prep1.1 loss-of-function caused significant apoptosis in the CNS. Hindbrain segmentation and patterning was affected severely, as revealed by either loss or defective expression of several hindbrain markers (foxb1.2/mariposa, krox20, pax2.1 and pax6.1), including anteriorly expressed Hox genes (hoxb1a, hoxa2 and hoxb2), the impaired migration of facial nerve motor neurons, and the lack of reticulospinal neurons (RSNs) except Mauthner cells. Furthermore, the heads of prep1.1 morphants lacked all pharyngeal cartilages. This was not caused by the absence of neural crest cells or their impaired migration into the pharyngeal arches, as shown by expression of dlx2 and snail1, but by the inability of these cells to differentiate into chondroblasts. Our results indicate that prep1.1 has a unique genetic function in craniofacial chondrogenesis and, acting as a member of Meinox-Pbc-Hox trimers, it plays an essential role in hindbrain development.

Animals↗
PubMed2003

The Mix family homeodomain gene bonnie and clyde functions with other components of the Nodal signaling pathway to regulate neural patterning in zebrafish.

Mix family homeodomain proteins, such as Xenopus Mixer and zebrafish Bonnie and clyde (Bon), have been shown to regulate the formation of the endoderm and are likely to be transcriptional mediators of Nodal signaling. Here, we show that, in addition to its previously described role in endoderm formation, Bon also regulates the anteroposterior patterning of the neuroectoderm. bon-mutant embryos exhibit an anterior reduction of the neural plate. By using targeted injection of antisense morpholino oligonucleotides, we demonstrate that Bon is required in the axial mesoderm for anterior neural development. Consistent with these results, bon-mutant embryos show defects in axial mesoderm gene expression starting at mid-gastrulation stages. In addition, genetic analyses demonstrate a functional interaction during neural patterning between bon and two components of the Nodal signaling pathway, the nodal-related gene squint (sqt) and forkhead box H1 [foxh1; mutant locus schmalspur (sur)]. bon-/-;sqt-/- and bon-/-;sur-/- embryos exhibit neural patterning defects that are much more severe than those seen in the single mutants, suggesting that these genes function in parallel in this process. We also show that the severity of the neural patterning defects in the single- and double-mutant embryos correlates with the degree of reduction in expression of the Wnt antagonist gene dickkopf 1. Furthermore, bon-/-;sqt-/- and bon-/-;sur-/- embryos exhibit identical morphological and gene expression defects, suggesting, in part, that bon, sqt and sur (foxh1) play overlapping roles in neural patterning. Taken together, these results provide evidence for a complex genetic network in which bon functions both downstream of, and possibly in parallel to, Nodal signaling to regulate neural patterning via the modulation of mesendodermal gene expression.

Animals↗
PubMed2003

An expression pattern screen for genes involved in the induction of the posterior nervous system of zebrafish.

The posterior nervous system, including the hindbrain and the spinal cord, has been shown to be formed by the transformation of neural plate of anterior character by signals derived from non-axial mesoderm. Although secreted factors, such as fibroblast growth factors (FGFs), Wnts, retinoic acid (RA) and Nodal, have been proposed to be the posteriorizing factors, the mechanism how neural tissue of posterior character is induced and subsequently specified along the anteroposterior axis remains elusive. To identify intercellular signaling molecules responsible for posteriorization of the neural plate as well as to find molecules induced intracellularly by the posteriorizing signal in the caudal neural plate, we screened by in situ hybridization for genes specifically expressed in posterior tissues, including the posterior neural plate and non-axial mesoderm when posteriorization of the neural plate takes place. From a subtracted library differentiating anterior versus posterior neural plate, 420 cDNA clones were tested, out of which 76 cDNA fragments showed expression restricted to the posterior tissue. These clones turned out to represent 32 different genes, including one novel secreted factor and one transmembrane protein. Seven genes were induced by non-axial mesodermal implants and bFGF beads, suggesting that these are among the early-response genes of the posteriorizing signal. Thus, our approach employing cDNA subtraction and subsequent expression pattern screening allows us to clone candidate genes involved in a novel signaling pathway contributing to the formation of the posterior nervous system.

Animals↗
PubMed2002

Guidance of primordial germ cell migration by the chemokine SDF-1.

The signals directing primordial germ cell (PGC) migration in vertebrates are largely unknown. We demonstrate that sdf-1 mRNA is expressed in locations where PGCs are found and toward which they migrate in wild-type as well as in mutant embryos in which PGC migration is abnormal. Knocking down SDF-1 or its receptor CXCR4 results in severe defects in PGC migration. Specifically, PGCs that do not receive the SDF-1 signal exhibit lack of directional movement toward their target and arrive at ectopic positions within the embryo. Finally, we show that the PGCs can be attracted toward an ectopic source of the chemokine, strongly suggesting that this molecule provides a key directional cue for the PGCs.

Animals↗
PubMed2002

Zebrafish Smad7 is regulated by Smad3 and BMP signals.

Growth factors of the TGF-beta superfamily such as BMPs and Nodals are important signaling factors during all stages of animal development. Smad proteins, the cytoplasmic mediators of most TGF-beta signals in vertebrates, play central roles not only for transmission but also in controlling inductive TGF-beta signals by feedback regulation. Here, we describe cloning, expression pattern, transcriptional regulation, and functional properties of two novel zebrafish Smad proteins: the TGF-beta agonist Smad3b, and the anti-Smad Smad7. We show that zebrafish Smad3b, in contrast to the related zebrafish Smad2, can induce mesoderm independently of TGF-beta signaling. Although mammalian Smad3 was shown to inhibit expression of the organizer-specific genes goosecoid, zebrafish smad3b activates organizer genes such as goosecoid. Furthermore, we show that Smad3 and BMP signals activate smad7. Because Smad7 blocks distinct TGF-beta signals in early zebrafish development, our data provide hints for new roles of smad3 genes in the regulation and modulation of TGF-beta signals. In summary, our analyses point out differences of Smad3b and Smad2 functions in zebrafish and provide the first link of smad3 and smad7 function in context of vertebrate development.

Amino Acid Sequence↗