PubMed Health⌕ Search

Biomedical subjects

C B Kimmel

Publications and source records attributed to C B Kimmel.

At least 55 records · Page 3Linked to original sources
PubMed1991

The fub-1 mutation blocks initial myofibril formation in zebrafish muscle pioneer cells.

The earliest muscle in zebrafish arises from iterated sets of two to six cells in each somite, the muscle pioneers (MP). MP develop synchronously in young trunk myotomes adjacent to the notochord, precisely where the horizontal myoseptum will form. They elongate without cell fusion and differentiate hours earlier than surrounding cells, thus providing a simple and accessible system for in vivo study of myogenesis and muscle patterning. Before the MP form definitive myofibrils they assemble long bundles of actin-containing filaments, similar to "stress-fiber-like structures" reported by others. In fub-1 mutants, in which myofibrils are disorganized in all skeletal muscle cells, the MP appear and elongate normally, but ordered actin filament bundles are not seen. This defect could underlie the later myofibrillar ones, consistent with the proposal that actin filament bundles are essential for proper formation of the muscle contractile apparatus.

Actins↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Pathfinding and synapse formation in a zebrafish mutant lacking functional acetylcholine receptors.

We induced and characterized a recessive lethal mutation, nic-1, in zebrafish that blocks the function of muscle acetylcholine (ACh) receptors. Homozygous nic-1 embryos are nonmotile and fail to respond to exogenous application of cholinergic agonists, although their muscles contract in response to direct electrical stimulation. Moreover, we do not detect cell surface labeling by alpha-bungarotoxin or monoclonal antibodies that recognize the other three subunits of ACh receptors. Motoneurons, however, establish morphologically normal patterns of innervation and normal neuromuscular junctions. We suggest that neither transmitter-mediated nerve signaling nor any other aspect of ACh receptor function is required for the formation of appropriate nerve connections in this system.

Animals↗
PubMed1990

Organization of hindbrain segments in the zebrafish embryo.

To learn how neural segments are structured in a simple vertebrate, we have characterized the embryonic zebrafish hindbrain with a library of monoclonal antibodies. Two regions repeat in an alternating pattern along a series of seven segments. One, the neuromere centers, contains the first basal plate neurons to develop and the first neuropil. The other region, surrounding the segment boundaries, contains the first neurons to develop in the alar plate. The projection patterns of these neurons differ: those in the segment centers have descending axons, while those in the border regions form ventral commissures. A row of glial fiber bundles forms a curtain-like structure between each center and border region. Specific features of the individual hindbrain segments in the series arise within this general framework. We suggest that a cryptic simplicity underlies the eventual complex structure that develops from this region of the CNS.

Animals↗
PubMed1990

Cell movements during epiboly and gastrulation in zebrafish.

Beginning during the late blastula stage in zebrafish, cells located beneath a surface epithelial layer of the blastoderm undergo rearrangements that accompany major changes in shape of the embryo. We describe three distinctive kinds of cell rearrangements. (1) Radial cell intercalations during epiboly mix cells located deeply in the blastoderm among more superficial ones. These rearrangements thoroughly stir the positions of deep cells, as the blastoderm thins and spreads across the yolk cell. (2) Involution at or near the blastoderm margin occurs during gastrulation. This movement folds the blastoderm into two cellular layers, the epiblast and hypoblast, within a ring (the germ ring) around its entire circumference. Involuting cells move anteriorwards in the hypoblast relative to cells that remain in the epiblast; the movement shears the positions of cells that were neighbors before gastrulation. Involuting cells eventually form endoderm and mesoderm, in an anterior-posterior sequence according to the time of involution. The epiblast is equivalent to embryonic ectoderm. (3) Mediolateral cell intercalations in both the epiblast and hypoblast mediate convergence and extension movements towards the dorsal side of the gastrula. By this rearrangement, cells that were initially neighboring one another become dispersed along the anterior-posterior axis of the embryo. Epiboly, involution and convergent extension in zebrafish involve the same kinds of cellular rearrangements as in amphibians, and they occur during comparable stages of embryogenesis.

Animals↗
PubMed1990

Origin and organization of the zebrafish fate map.

We have analyzed lineages of cells labeled by intracellular injection of tracer dye during early zebrafish development to learn when cells become allocated to particular fates during development, and how the fate map is organized. The earliest lineage restriction was described previously, and segregates the yolk cell from the blastoderm in the midblastula. After one or two more cell divisions, the lineages of epithelial enveloping layer (EVL) cells become restricted to generate exclusively periderm. Following an additional division in the late blastula, deep layer (DEL) cells generate clones that are restricted to single deep embryonic tissues. The appearance of both the EVL and DEL restrictions could be causally linked to blastoderm morphogenesis during epiboly. A fate map emerges as the DEL cell lineages become restricted in the late blastula. It is similar in organization to that of an amphibian embryo. DEL cells located near the animal pole of the early gastrula give rise to ectodermal fates (including the definitive epidermis). Cells located near the blastoderm margin give rise to mesodermal and endodermal fates. Dorsal cells in the gastrula form dorsal and anterior structures in the embryo, and ventral cells in the gastrula form dorsal, ventral and posterior structures. The exact locations of progenitors of single cell types and of local regions of the embryo cannot be mapped at the stages we examined, because of variable cell rearrangements during gastrulation.

Animals↗
PubMed1990

Expression of a homeobox gene product in normal and mutant zebrafish embryos: evolution of the tetrapod body plan.

An antibody was used to detect antigens in zebrafish that appear to be homologous to the frog homeodomain-containing protein XlHbox 1. These antigens show a restricted expression in the anteroposterior axis and an anteroposterior gradient in the pectoral fin bud, consistent with the distribution of XlHbox 1 protein in frog and mouse embryos. In the somitic mesoderm, a sharp anterior limit of expression coincides exactly with the boundary between somites 4 and 5, and the protein level fades out posteriorly. A similar, graded expression of the antigen is seen within the series of Rohon-Beard sensory neurons of the CNS. We also immunostained the mutant spt-1 ('spadetail'), in which the trunk mesoderm is greatly depleted and disorganized in the region of XlHbox 1 expression. The defects stem from misdirected cell movements during gastrulation, but nervertheless, newly recruited cells that partially refill the trunk mesoderm express the antigen within the normal span of the anteroposterior axis. This finding suggests that the mutation does not delete positional information required for activation of the XlHbox 1 gene.

Animals↗
PubMed1990

Primary neurons that express the L2/HNK-1 carbohydrate during early development in the zebrafish.

In zebrafish, many nerve pathways in both the CNS and periphery are pioneered by a small and relatively simple set of 'primary' neurons that arise in the early embryo. We now have used monoclonal antibodies to show that, as they develop, primary neurons of several functional classes express on their surfaces the L2/HNK-1 tetrasaccharide that is associated with a variety of cell surface adhesion molecules. We have studied the early labeling patterns of these neurons, as well as some non-neural cells, and found that the time of onset and intensity of immunolabeling vary specifically according to cell type. The first neuronal expression is by Rohon-Beard and trigeminal ganglion neurons, both of which are primary sensory neurons that mediate touch sensitivity. These cells express the epitope very strongly on their growth cones and axons, permitting study of their development unobscured by labeling in other cells. Both types initiate axogenesis at the same early time, and appear to be the first neurons in the embryo to do so. Their peripheral neurites display similar branching patterns and have similar distinctive growth cone morphologies. Their central axons grow at the same rate along the same longitudinal fiber pathway, but in opposite directions, and where they meet they appear to fasciculate with one another. The similarities suggest that Rohon-Beard and trigeminal ganglion neurons, despite their different positions, share a common program of early development. Immunolabeling is also specifically present on a region of the brain surface where the newly arriving trigeminal sensory axons will enter the brain. Further, the trigeminal expression of the antigen persists in growth cones during the time that they contact an individually identified central target neuron, the Mauthner cell, which also expresses the epitope. These findings provide descriptive evidence for possible roles of L2/HNK-1 immunoreactive molecules in axonal growth and synaptogenesis.

Animals↗
PubMed1989

A mutation that changes cell movement and cell fate in the zebrafish embryo.

The study of developmental patterning has been facilitated by the availability of mutations that produce changes in cell fate, in animals such as Caenorhabditis elegans and Drosophila melanogaster. We now describe a zygotic lethal mutation in the zebrafish, Brachydanio rerio, that also changes how particular embryonic cells develop. Severe pattern deficiencies are observed that are restricted to a single body region, the trunk. The mutation may directly affect mesoderm, as somites do not form in the trunk. Head and tail structures, including tail somites, are relatively undisturbed. The earliest detected expression of the mutation is during gastrulation, when movements of mesodermal cells occur incorrectly. We injected prospective trunk mesodermal cells with lineage tracer dye and observed that in mutants these cells may enter a new body region, the tail, and there may express a new fate appropriate for the changed position.

Animals↗
PubMed1989

Genetics and early development of zebrafish.

Zebrafish genes and development are being studied in a growing number of laboratories. Given that many other organisms are already being exploited by large numbers of investigators, and that our general knowledge about the zebrafish embryo and genome is at present rather sketchy, why should we now concern ourselves with how this tropical fish develops? Whereas the zebrafish embryo is similar in important ways to other vertebrate embryos, it is relatively simple and unusually accessible for both cellular and genetic analyses.

Animals↗
PubMed1988

A neural degeneration mutation that spares primary neurons in the zebrafish.

We describe an embryonic lethal mutation in the zebrafish Brachydanio rerio that specifically affects the viability of most cells in the embryonic central nervous system (CNS). The mutation ned-1 (b39rl) was induced with gamma-irradiation and segregates as a single recessive allele closely linked to its centromere. It produces massive cell death in the CNS but a small set of specific neurons, including Rohon-Beard sensory neurons, large hindbrain interneurons, and primary motoneurons, survive embryogenesis and are functional. Synaptic connections between embryonic motoneurons and muscle cells appear physiologically normal, and the normally observed spontaneous flexions are present. Correlated with the presence of sensory neurons and interneurons, mutant embryos display reflexive movements in response to mechanical stimulation. Together, the surviving neurons, called primary neurons, form a class of cells that are prominent in size and arise early during development. Thus, this mutation may define a function that is differentially required by developmentally distinguishable sets of cells in the embryonic CNS.

Animals↗
PubMed1988

Segmental pattern of development of the hindbrain and spinal cord of the zebrafish embryo.

In the ventral hindbrain and spinal cord of zebrafish embryos, the first neurones that can be identified appear as single cells or small clusters of cells, distributed periodically at intervals equal to the length of a somite. In the hindbrain, a series of neuromeres of corresponding length is present, and the earliest neurones are located in the centres of each neuromere. Young neurones within both the hindbrain and spinal cord were identified in live embryos using Nomarski optics, and histochemically by labelling for acetylcholinesterase activity and expression of an antigen recognized by the monoclonal antibody zn-1. Among them are individually identified hindbrain reticulospinal neurones and spinal motoneurones. These observations suggest that early development in these regions of the CNS reflects a common segmental pattern. Subsequently, as more neurones differentiate, the initially similar patterning of the cells in these two regions diverges. A continuous longitudinal column of developing neurones appears in the spinal cord, whereas an alternating series of large and small clusters of neurones is present in the hindbrain.

Acetylcholinesterase↗
PubMed1988

Development of segmentation in zebrafish.

Recent findings on the nature and origin of segmentation in zebrafish, Brachydanio rerio, are reviewed. Segmented peripheral tissues include the trunk and tail myotomes, that are derived from somitic mesoderm, and the pharyngeal arches that are derived from head mesoderm in addition to other sources. Two major regions of the central nervous system, the spinal cord and hindbrain, are also segmentally organized, as deduced from the distribution of identified neurones in both regions and by formation of neuromeres in the hindbrain that contain single sets of these neurones. Neural and mesodermal segments in the same body region can be related to one another by their patterns of motor innervation. This relationship is simple for the spinal/myotomal segments and complex for the hindbrain/pharyngeal arch segments. Development of the segments is also complex. Mesodermal and ectodermal progenitors have separate embryonic origins and indeterminate cell lineages, and the embryonic cells migrate extensively before reaching their definitive segmental positions. Results of heat-shock experiments suggest that development of myotomal and spinal segments are regulated coordinately in postgastrula embryos. Segmental patterning may be a relatively late feature of zebrafish embryonic development.

Animals↗