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Biomedical subjects

C I Bargmann

Publications and source records attributed to C I Bargmann.

At least 55 records · Page 3Linked to original sources

Cell fate specification and differentiation in the nervous system of Caenorhabditis elegans.

Neuronal cell fates are specified by a hierarchy of events mediated by cell-intrinsic determinants and cell-cell interactions. The determination of cell fate can be subdivided into three general steps. First, cell fate is restricted by the cell's position in the animal. For example, neurons are specified along the anterior-posterior body axis through the action of the Hox genes lin-39, mab-5, and egl-5. Second, a decision is made to generate a particular cell type, such as the progenitor of a neurogenic lineage as opposed to that of an epidermal lineage. Among the genes that influence this decision is the proneural gene lin-32. Third, characteristics of a particular cell type are specified. For example, in a neurogenic lineage, a decision may be made to generate a specific neuron type such as a sensory or motor neuron. Genes that affect neuronal fate can act in different ways to influence the development of different types of neurons.

Animals↗

A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans.

In vertebrate visual and olfactory systems, a cyclic nucleotide-gated channel couples receptor activation to electrical activity of the sensory neurons. The Caenorhabditis elegans tax-2 gene is required for some forms of olfaction, for chemosensation of salts, and for thermosensation. We show here that tax-2 encodes a predicted subunit of a cyclic nucleotide-gated channel that is expressed in olfactory, gustatory, and thermosensory neurons, implicating this channel in multiple sensory modalities. Some sensory neurons display axon outgrowth defects in tax-2 mutants. Thus, the channel has an unexpected role in sensory neuron development in addition to its role in sensation. Consistent with this proposed dual function, a Tax-2::GFP fusion protein is present both in sensory cilia and in sensory axons.

Alleles↗

The C. elegans gene vab-8 guides posteriorly directed axon outgrowth and cell migration.

The assembly of the nervous system in the nematode C. elegans requires the directed migrations of cells and growth comes along the anteroposterior and dorsoventral body axis. We show here that the gene vab-8 is essential for most posteriorly directed migrations of cells and growth cones. Mutations in vab-8 disrupt fourteen of seventeen posteriorly directed migrations, but only two of seventeen anteriorly directed and dorsoventral migrations. For two types of neurons that extend axons both anteriorly and posteriorly, vab-8 mutations disrupt only the growth of the posteriorly directed axon. vab-8 encodes two genetic activities that function in the guidance of different migrations. Our results suggest that most posteriorly directed cell and growth cone migrations are guided by a common mechanism involving the vab-8 gene.

Alleles↗

Mechanosensory signalling in C. elegans mediated by the GLR-1 glutamate receptor.

NEURONAL signalling across synapses involves activation of many neurotransmitter receptors on postsynaptic cells. glr-1 encodes a potential glutamate receptor in the nematode Caenorhabditis elegans which is most similar to vertebrae AMPA-type ionotropic glutamate receptors. glr-1 is expressed in motor neurons and interneurons, including interneurons implicated in the control of locomotion. Here we investigate the contribution of glr-1 to the normal signalling of these neurons, by generating a deletion mutation in glr-1. We find that mutant worms are deficient in their ability to withdraw backwards when mechanically stimulated, but they withdraw normally in response to chemical repellents. The ASH sensory neurons mediate withdrawal responses both to mechanical stimuli and to repellents, and ASH makes chemical synapses with glr-1-expressing interneurons. Our results suggest that postsynaptic interneurons use different neurotransmitter receptors to process two sensory stimuli detected by one sensory neuron.

Amino Acid Sequence↗

Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans.

Using their senses of taste and smell, animals recognize a wide variety of chemicals. The nematode C. elegans has only fourteen types of chemosensory neurons, but it responds to dozens of chemicals, because each chemosensory neuron detects several stimuli. Here we describe over 40 highly divergent members of the G protein-coupled receptor family that could contribute to this functional diversity. Most of these candidate receptor genes are in clusters of two to nine similar genes. Eleven of fourteen tested genes appear to be expressed in small subsets of chemosensory neurons. A single type of chemosensory neuron can potentially express at least four different receptor genes. Some of these genes might encode receptors for water-soluble attractants, repellents, and pheromones.

1-Octanol↗

Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans.

Following prolonged exposure to an odorant, C. elegans exhibits a diminished response to the odorant for several hours. This olfactory adaptation is odorant selective; animals can adapt independently to different odorants sensed by a single pair of olfactory neurons, the AWC neurons. The mechanism of olfactory adaptation is genetically complex, with different genes required for adaptation to different odorants. Animals mutant for the gene adp-1 fail to adapt to a subset of AWC-sensed odorants; adp-1 affects a calcium-dependent process required for adaptation. Mutations in another gene, osm-9, affect adaptation to a different but overlapping subset of AWC-sensed odorants. Mutations in adp-1 and osm-9 do not diminish the ability of unadapted animals to respond to odorants, indicating that odorant sensation and odorant adaptation are distinct processes.

Adaptation, Physiological↗

The C. elegans gene odr-7 encodes an olfactory-specific member of the nuclear receptor superfamily.

Olfactory discrimination is achieved through the action of olfactory neurons with diverse chemical specificities. In C. elegans, at least ten different types of chemosensory neurons respond to different chemicals. The odr-7 gene is required for the function of one pair of chemosensory neurons called AWA neurons. odr-7 null mutants fail to respond to all odorants detected by the AWA neurons, while a missense mutation in odr-7 causes a specific defect in one odorant response. odr-7 encodes a protein with similarity to the DNA-binding domain of the nuclear receptor genes; it is expressed predominantly in the AWA neurons. odr-7 may regulate the expression of olfactory signaling molecules that define a single type of olfactory neuron.

Amino Acid Sequence↗

Odorant-selective genes and neurons mediate olfaction in C. elegans.

Olfaction is a versatile and sensitive mechanism for detecting volatile odorants. We show that the nematode C. elegans detects many volatile chemicals, which can be attractants, repellents, or attractants at low concentrations and repellents at high concentrations. Through laser ablation, we have identified chemosensory neurons that detect volatile odorants. Chemotaxis to volatile odorants requires different sensory neurons from chemotaxis to water-soluble attractants, indicating that C. elegans might have senses that correspond to smell and taste, respectively. Single neurons have complex sensory properties, since six distinguishable volatile odorants are sensed by only two types of sensory neurons. Chemotaxis to subsets of volatile odorants is disrupted by mutations in the odr genes, which might be involved in odorant sensation or signal transduction.

Animals↗

The cellular and genetic basis of olfactory responses in Caenorhabditis elegans.

The small soil nematode Caenorhabditis elegans has only 302 neurons in its entire nervous system, so it is possible to analyse the functions of individual neurons in the animal's behaviour. We are using behavioural, cellular and genetic analyses of chemotactic responses to find out how olfactory behaviour patterns are generated and regulated. Single chemosensory neurons in C. elegans can recognize several different attractive odorants that are distinguished by the animal. Distinct sets of chemosensory neurons detect high and low concentrations of a single odorant. Odorant responses adapt after prolonged exposure to an odorant; this adaptation is odorant specific and reversible. Mutants with defects in odorant responses have been identified. Some genes appear to be necessary for the development or function of particular kinds of sensory neurons. Other genes have effects that suggest that they participate in odorant reception or signal transduction.

Adaptation, Physiological↗

The Caenorhabditis elegans unc-31 gene affects multiple nervous system-controlled functions.

We have devised a method for selecting Caenorhabditis elegans mutants that execute feeding motions in the absence of food. One mutation isolated in this way is an allele of the gene unc-31, first discovered by S. Brenner in 1974, because of its effects on locomotion. We find that strong unc-31 mutations cause defects in four functions controlled by the nervous system. Mutant worms are lethargic, feed constitutively, are defective in egg-laying and produce dauer larvae that fail to recover. We discuss two extreme models to explain this pleiotropy: either unc-31 affects one or a few neurons that coordinately control several different functions, or it affects many neurons that independently control different functions.

Animals↗

Control of larval development by chemosensory neurons in Caenorhabditis elegans.

Larval development of the nematode Caenorhabditis elegans is controlled by the activities of four classes of chemosensory neurons. The choice between normal development and development into a specialized larval form called a dauer larva is regulated by competing environmental stimuli: food and a dauer pheromone. When the neuron classes ADF, ASG, ASI, and ASJ are killed, animals develop as dauer larvae regardless of environmental conditions. These neurons might sense food or dauer pheromone, or both, to initiate the specialized differentiation of many cell types that occurs during dauer formation. Entry into and exit from the dauer stage are primarily controlled by different chemosensory neurons. The analysis of mutants defective in dauer formation indicates that the chemosensory neurons are active in the absence of sensory inputs and that dauer pheromone inhibits the ability of these neurons to generate a signal necessary for normal development.

Animals↗

Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans.

The functions of the 11 classes of exposed chemosensory neurons of C. elegans were tested by killing cells with a laser microbeam. One pair of neurons, the ASE neurons, is uniquely important for chemotaxis: killing the ASE neurons greatly reduced chemotaxis to cAMP, biotin, Cl-, and Na+. Additional chemosensory function is distributed among several other cell types. Thus, 3 pairs of chemosensory neurons (ADF, ASG, and ASI) contribute to a residual response to cAMP, biotin, Cl-, and Na+ after ASE is killed. Chemotaxis to lysine similarly depends on the partly redundant functions of 4 pairs of chemosensory neurons (ASE, ASG, ASI, and ASK). The combined activity of several neuron types that act in parallel might increase the fidelity of chemotaxis.

Animals↗