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K Hatta

Publications and source records attributed to K Hatta.

At least 55 records · Page 3Linked to original sources

Role of the floor plate in axonal patterning in the zebrafish CNS.

To determine the role of the floor plate (FP) in CNS development, I have used labeling techniques, including immunolabeling, to analyze cyclops mutant embryos, which lack the FP. Except for the anterior brain, the mutant phenotype is almost exclusively confined to the vicinity of the ventral CNS midline. In the midbrain, the number of ventral neurons is reduced and cell patterning is disturbed. In contrast, the neuronal arrangement in the spinal cord is almost normal, including in particular both primary and secondary motoneurons. Longitudinal axonal bundles are disorganized in both the brain and spinal cord. Laser ablating the FP in wild-type embryos locally phenocopies cyclops axonal disturbances, and transplanting wild-type FP precursor cells into mutants locally rescues the disturbances. These results demonstrate a significant role for the FP in pathfinding and fasciculation by axons in situ, especially during their longitudinal courses.

Animals↗

3-((+/-)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) more potently antagonizes the high-affinity Mg2+ binding site on the N-methyl-D-aspartate/phencyclidine receptor ion channel complex than the L-glutamate recognition site.

Using frozen-thawed and extensively washed rat cortical membranes, the effects of 3-((+/-)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) on [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine ([3H]TCP) binding stimulated by either 1 microM L-glutamate or 300 microM Mg2+ were examined. CPP much more potently inhibited Mg(2+)-stimulated [3H]TCP binding than [3H]TCP binding stimulated by L-glutamate, suggesting that CPP preferentially acts at Mg2+ recognition sites with high affinity, which may be anatomically and/or functionally associated with a recognition site for N-methyl-D-asparate (NMDA) antagonists.

Animals↗

The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system.

The floor plate is a set of epithelial cells present in the ventral midline of the neural tube in vertebrates that seems to have an important role in the developmental patterning of central nervous system fibre pathways, and arrangements of specific neurons. The floor plate arises from dorsal ectodermal cells closely associated with the mesoderm that forms notochord, and it may depend on interactions from the notochord for its specification. To learn the nature of these interactions we have analysed mutations in zebrafish (Brachydanio rerio). We report here that in wild-type embryos the floor plate develops as a simply organized single cell row, but that its development fails in embryos bearing the newly discovered zygotic lethal 'cyclops' mutation, cyc-1(b16). Mosaic analysis establishes that cyc-1 blocks floor plate development autonomously and reveals the presence of homeogenetic induction between floor plate cells.

Animals↗

Modulation of Mg(2+)-dependent [3H]TCP binding by L-glutamate, glycine, and guanine nucleotides in rat cerebral cortex.

Biochemical and electrophysiological studies have demonstrated that phencyclidine (PCP) recognition site exists in the ion channel of the N-methyl-D-aspartate (NMDA) receptor ion channel complex. Using an extensively washed rat cortical membrane preparation, the effects of Mg2+ and guanylylimidodiphosphate (GppNHp) were examined on the binding of [3H]-N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP). Low concentrations of Mg2+ (EC50 = 11 microM) stimulated [3H]TCP binding under the basal condition and high concentrations of Mg2+ (IC50 = 1 mM) inhibited it. In the presence of 10 microM L-glutamate and 10 microM glycine, their EC50 values for Mg2+ enhancement of [3H]TCP binding were markedly reduced (to 1.9 microM or 8.4 microM), respectively. By contrast, the IC50 values for Mg2+ inhibition of [3H]TCP binding were reduced in the presence of L-glutamate, but not glycine. Furthermore, a stimulatory effect of Mg2+ on [3H]TCP binding was additional to the [3H]TCP binding stimulated by a maximally effective concentration of L-glutamate (10 microM) or glycine (10 microM). In the kinetic study, 300 microM Mg2+ produced an increase in the rates of both association and dissociation of [3H]TCP. Similar results were obtained with L-glutamate (10 microM) and glycine (10 microM); 10 mM Mg2+ also caused an acceleration of the association rate but strongly decreased [3H]TCP binding at equilibrium. Compared with [3H]TCP binding under the basal condition, K+ (10 mM) alone decreased the maximal binding without producing any change in the association rate; 10 mM K+ also significantly decreased Mg(2+)-stimulated [3H]TCP binding but caused no change in the acceleration of the association rate caused by Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diversity of expression of engrailed-like antigens in zebrafish.

We have studied developmental expression of zebrafish engrailed-like (Eng) antigens. Many cell types are reproducibly labeled by two antibodies that recognize the Eng homeodomain, but other cells are labeled by only one or the other, suggesting a hitherto unrecognized complexity of Eng proteins. Expression patterns vary remarkably according to cell type and location. In the undifferentiated primordia of the brain and of each myotome, expression by a stripe of cells spatially subdivides the primordium at a location where a morphological boundary forms later, suggesting expression may be required for development of the boundaries. Supporting this hypothesis, trunk myotomal cells that express Eng are absent in spt-1 mutant embryos, just where the myotomal boundaries fail to form. Another pattern is present in rhombomeres, pharyngeal arches, and the pectoral girdle. In each of these cases, cells (neuron, muscle, cartilage) generating a subset of a series of repeated elements selectively express Eng. These subsets then form specialized derivatives, suggesting Eng homeoproteins are involved in determining the specializations. Epidermal expression is present in the ventral half of the pectoral fin rudiment, precisely 'compartmentalizing' the fin. Neuronal cells at a certain dorsoventral level in each hindbrain and spinal cord segment selectively express Eng, suggesting segmental control of neuronal identity. Specific expression patterns are observed in taste buds, otic vesicles and teeth. Thus we propose that eng genes function in diverse cell types in zebrafish, but play selector roles that can be classified into a few basic types.

Animals↗

Genetic control of primary neuronal development in zebrafish.

During the first day of embryogenesis in the zebrafish, a precise and relatively simple network of neurons develops, pioneering axonal pathways and apparently functioning to mediate reflexive motor responses to touch stimuli. We have begun to use zygotic lethal mutations to analyze the assembly of this 'primary' embryonic nervous system. Here we focus on spinal primary motoneurons, their inputs from hindbrain Mauthner neurons, and their outputs to segmental body wall muscle. The mutation nic-1 blocks synaptic transmission between nerve and muscle, yet embryonic primary motoneurons appear normal, suggesting that functional interactions with their targets are not involved in regulating their development. The mutation spt-1 directly disrupts development of this muscle, and the mutation cyc-1 appears to directly block specification of the floor plate. Both spt-1 and cyc-1 affect aspects of primary neuronal development, and they probably do so indirectly. The nonautonomous actions of these mutations are local and they produce variable neuronal phenotypes. The observations can be interpreted to mean that some cellular interactions that specify the neurons and their axonal paths occur at close range and involve multiple, possibly combinatorial, transmitter-independent pathways.

Animals↗

Specification of jaw muscle identity in zebrafish: correlation with engrailed-homeoprotein expression.

Molecules that determine the specific features of individual muscles in vertebrates are unknown. Antibody labeling studies described here revealed a molecular difference among muscles in the zebrafish head, in that two functionally related jaw muscles (the levator arcus palatini and the dilator operculi), and not other head muscles, expressed engrailed-homeodomain proteins. Expression began in mesoderm-derived muscle-precursor cells in the paraxial mesenchyme and continued during muscle morphogenesis and differentiation. Growth cones of trigeminal motoneurons that innervate these muscles associated with the precursors within a few hours of the time they began to express engrailed. It is proposed that the engrailed proteins in these cells establish muscle identity and neuromuscular target recognition.

Animals↗

Biphasic effects of magnesium on the [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine binding in the rat cerebral cortex.

Mg2+ at micromolar concentrations greatly enhanced [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes, whereas [3H]TCP binding was inhibited by Mg2+ at concentrations higher than 1 mM. In the presence of either L-glutamate (10 microM) or glycine (10 microM), 30 microM Mg2+ caused further stimulation of [3H]TCP binding, suggesting that a high-affinity site for Mg2+ is distinct from the glutamate or glycine binding site. These findings indicate that Mg2+ acts on at least two different recognition sites, e.g. a novel high-affinity site for Mg2+ which stimulates [3H]TCP binding and the Mg2+ recognition site located within the ion channel.

Animals↗

Early axonal contacts during development of an identified dendrite in the brain of the zebrafish.

We have identified the initial synaptic contacts made onto the Mauthner (M) cell, an identified neuron that arises during early development of the zebrafish hindbrain. The contacts are made by a small bundle of pioneering trigeminal sensory axons onto the M cell soma before it forms dendrites. The sensory bundle is then partially enveloped by the M cell. The lateral dendrite appears at about the site of the contact, and eventually the trigeminal inputs are shifted to its trunk. As the dendrite elongates, other sensory contacts are made on its distal regions, sequentially from the acoustico-vestibular nerve and the lateral line nerves. To learn whether the earliest inputs induce the initial outgrowth of the M cell dendrite, we ablated the trigeminal neurons by laser irradiation before they contacted the M cell. Morphogenesis of the M cell, including its dendrite, appeared normal.

Afferent Pathways↗

Neural cadherin: role in selective cell-cell adhesion.

Cadherins are a family of Ca2+-dependent intercellular adhesion molecules. Complementary DNAs encoding mouse neural cadherin (N-cadherin) were cloned, and the cell binding specificity of this molecule was examined. Mouse N-cadherin shows 92 percent similarity in amino acid sequence to the chicken homolog, while it shows 49 percent and 43 percent similarity to epithelial cadherin and to placental cadherin of the same species, respectively. In cell binding assays, mouse N-cadherin did not cross-react with other mouse cadherins, but it did cross-react with chicken N-cadherin. The results indicate that each cadherin type confers distinct adhesive specificities on different cells, and also that the specificity of N-cadherin is conserved between mammalian and avian cells.

Amino Acid Sequence↗

Cadherin-mediated specific cell adhesion and animal morphogenesis.

Cadherins are a family of transmembrane glycoproteins which are responsible for Ca2+-dependent cell-cell adhesion. Each member of the family displays a unique pattern of tissue distribution. The expression of cadherin molecules in an embryo is spatiotemporally regulated so as to be associated with a variety of morphogenetic events. Antibodies against cadherins perturb the morphogenesis of tissues, indicating their importance in tissue formation. When cells were transfected with cDNAs encoding cadherins, they expressed the exogenous cadherin molecules and these were functional. Using these transfected cells, we tested whether each member of the cadherin family has a binding specificity, and found that cells preferentially adhere to those expressing the identical cadherin type. The cadherin-mediated specific adhesion also occurred in the attachment of neurites to the surface of other cells. These observations suggest that cadherins are crucial for the selective adhesiveness of cells, and thus for the embryonic morphogenetic processes in which specific adhesive interactions of cells are involved.

Animals↗

[Problems of diagnosis and surgical treatment in pleural mesothelioma].

Twelve patients with pleural mesothelioma were operated on over a period of 6 years. Two of six patients with localized type died of recurrence. One of two patients showed fibrous form with low grade malignancy and the other showed a mixed type on their histological examination. The remaining 4 patients are alive and well with the combined resection of the tumor and the chest wall for the past 2 to 3 years. Three of six patients with diffuse type had an operation of pleuropneumonectomy with the resection of adjacent structures such as the diaphragm, SVC and the chest wall. One of them who had had the implantation at the chest wall where the biopsy needle entered, developed peritoneal mesothelioma. At laparotomy, numerous nodules were found. He was given 470 mg of CDDP and 80 mg of ADM into the cavity through the tubes. Though this patient died eventually, nodules were found to be macroscopically disappeared at autopsy. But they were left in the area where the drugs could not reach. The other two patients are alive and well for 16 to 22 months after the operation. The remaining 3 patients, who did not have the diagnosis preoperatively, died of cardio-pulmonary insufficiency due to local compression by the huge tumor at 3 months, 7 months and 2 years respectively after the exploratory thoracotomy. It is concluded that wide resection including the rib for a case with solitary lesion and early thoracotomy for a case with undiagnosed chest fluid, followed by pleuropneumonectomy or pleurectomy and post-operative local chemotherapy, are recommended for this malignant disease.

Adult↗

Guidance of optic nerve fibres by N-cadherin adhesion molecules.

The dendritic branches (neurites) of developing neurons migrate along specific pathways to reach their targets. It has been suggested that this migration is guided by factors present on the surface of other neurons or glial cells. The molecular nature of such factors, however, remains to be elucidated. N-cadherin is a cell-surface glycoprotein which belongs to the cadherin family of cell-cell adhesion molecules. This adhesion molecule is expressed in various neuronal cells as well as in glial cells of the central and peripheral nervous systems in vertebrate embryos and recent immunological studies suggested that N-cadherin may play a role in guiding the migration of neurites on myotubes or astrocytes. To further examine this possibility, we used a molecular-genetic approach; that is, we examined the outgrowth of chicken embryonic optic axons on monolayer cultures of Neuro 2a or L cells transfected with the complementary DNA encoding chicken N-cadherin. The data indicate that N-cadherin is used as a guide molecule for the migration of optic axons on cell surfaces.

Animals↗

Role of N-cadherin cell adhesion molecules in the histogenesis of neural retina.

We investigated the role of N-cadherin cell adhesion molecules in the histogenesis of the chicken neural retina. In the undifferentiated retina of early embryos, N-cadherin is almost evenly distributed. With differentiation, N-cadherin was gradually localized in particular cell layers. In the 8.5 to 10.5 day embryos, N-cadherin was most abundant in the optic nerve fiber layer, the plexiform layers and the outer limiting membrane. Thereafter, this molecule gradually diminished from most parts of the retina, except in the outer limiting membrane. When incubated with Fab fragments of a polyclonal antibody to N-cadherin, retinas of early embryos tended to dissociate and could not be maintained as a tissue mass. Retinas from older embryos were not dissociated by the Fab, but their morphogenesis was severely affected. We conclude that N-cadherin is essential for maintaining the overall structure of the undifferentiated retina, but during development, its role becomes restricted to maintaining more specific regions of the tissue. We also suggest that there might be additional, unidentified cadherin-like molecules in the retina.

Animals↗

Identification of a gene family of cadherin cell adhesion molecules.

Cadherins are a group of functionally related glycoproteins responsible for the Ca2+-dependent cell-cell adhesion mechanism. They are divided into subclasses, such as E-, P- and N-cadherin, which are distinct in immunological specificities and tissue distribution. Cell aggregation experiments suggest that these molecules have subclass specificities in cell-cell binding and are involved in selective cell adhesions. Analysis of amino acid sequences deduced from the nucleotide sequences of cDNAs encoding cadherins demonstrated that they are integral membrane proteins and share common sequences throughout their entire length; average similarity in the sequences among them is in a range of 50-60%. This result provided evidence that cadherins constitute a gene family which encodes adhesion molecules with different specificities. We also showed that, when cells with little cadherin activity were transfected with cadherin cDNAs, they acquired the cadherin-mediated adhesion properties.

Animals↗