Variable cell number in nematodes.
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Animals↗
Biomedical subjects
S W Emmons
Publications and source records attributed to S W Emmons.
Signal transduction. Mating, channels and kidney cysts.
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Animals↗
Patterning of Caenorhabditis elegans posterior structures by the Abdominal-B homolog, egl-5.
The Caenorhabditis elegans body axis, like that of other animals, is patterned by the action of Hox genes. In order to examine the function of one C. elegans Hox gene in depth, we determined the postembryonic expression pattern of egl-5, the C. elegans member of the Abdominal-B Hox gene paralog group, by means of whole-mount staining with a polyclonal antibody. A major site of egl-5 expression and function is in the epithelium joining the posterior digestive tract with the external epidermis. Patterning this region and its derived structures is a conserved function of Abd-B paralog group genes in other animals. Cells that initiate egl-5 expression during embryogenesis are clustered around the presumptive anus. Expression is initiated postembryonically in four additional mesodermal and ectodermal cell lineages or tissues. Once initiated in a lineage, egl-5 expression continues throughout development, suggesting that the action of egl-5 can be regarded as defining a positional cell identity. A variety of cross-regulatory interactions between egl-5 and the next more anterior Hox gene, mab-5, help define the expression domains of their respective gene products. In its expression in a localized body region, function as a marker of positional cell identity, and interactions with another Hox gene, egl-5 resembles Hox genes of other animals. This suggests that C. elegans, in spite of its small cell number and reproducible cell lineages, may not differ greatly from other animals in the way it employs Hox genes for regional specification during development.
Animals↗
Patterning of dopaminergic neurotransmitter identity among Caenorhabditis elegans ray sensory neurons by a TGFbeta family signaling pathway and a Hox gene.
We have investigated the mechanism that patterns dopamine expression among Caenorhabditis elegans male ray sensory neurons. Dopamine is expressed by the A-type sensory neurons in three out of the nine pairs of rays. We used expression of a tyrosine hydroxylase reporter transgene as well as direct assays for dopamine to study the genetic requirements for adoption of the dopaminergic cell fate. In loss-of-function mutants affecting a TGFbeta family signaling pathway, the DBL-1 pathway, dopaminergic identity is adopted irregularly by a wider subset of the rays. Ectopic expression of the pathway ligand, DBL-1, from a heat-shock-driven transgene results in adoption of dopaminergic identity by rays 3-9; rays 1 and 2 are refractory. The rays are therefore prepatterned with respect to their competence to be induced by a DBL-1 pathway signal. Temperature-shift experiments with a temperature-sensitive type II receptor mutant, as well as heat-shock induction experiments, show that the DBL-1 pathway acts during an interval that extends from two to one cell generation before ray neurons are born and begin to differentiate. In a mutant of the AbdominalB class Hox gene egl-5, rays that normally express EGL-5 do not adopt dopaminergic fate and cannot be induced to express DA when DBL-1 is provided by a heat-shock-driven dbl-1 transgene. Therefore, egl-5 is required for making a subset of rays capable of adopting dopaminergic identity, while the function of the DBL-1 pathway signal is to pattern the realization of this capability.
Animals↗
Regulated nuclear entry of the C. elegans Pax-6 transcription factor.
It is shown that the C. elegans Pax-6 locus encodes two protein isoforms. One contains a Paired DNA binding domain as well as a homeodomain; the other consists only of the carboxy-terminal portion of the locus encoding the homeodomain. These two isoforms are expressed in a variety of postembryonic cell lineages. In one set of lineages, nuclear localization of a homeodomain-only form (MAB-18 isoform) appears to be under temporal and spatial control. Nuclear localization of MAB-18 is correlated with the genetic requirement for mab-18 and with activation of a reporter gene driven by a mab-18 promoter. Reporter gene expression is dependent on mab-18 gene activity. It is hypothesized that a positive feedback loop is activated by regulated nuclear entry.
Animals↗
Worms as an evolutionary model.
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Animals↗
Specification of sense-organ identity by a Caenorhabditis elegans Pax-6 homologue.
The Pax-6 transcription-factor gene, containing a paired domain and a paired-type homeodomain, is conserved in structure and ubiquitously present among Metazoa. It is required for development of the central nervous system, and is mutated in human aniridia, mouse and rat small eye and Drosophila eyeless. We identified the Pax-6 gene of the nematode Caenorhabditis elegans in genetic studies of male tail morphology. C. elegans Pax-6 encodes at least two independent genetic functions. One, like other Pax-6 genes, contains paired and homeodomains; this constitutes the genetic locus vab-3. The other, described here, is expressed from an internal promoter and contains only the homeodomain portion; this constitutes the genetic locus mab-18. The mab-18 form of the gene is expressed in a peripheral sense organ and is necessary for specification of sense-organ identity. Its function in this context could be to regulate the expression of cell recognition and adhesion proteins required for sense-organ assembly.
Amino Acid Sequence↗
A transcription factor controlling development of peripheral sense organs in C. elegans.
The basic-helix-loop-helix (bHLH) proteins constitute a class of transcription factors thought to be important in the control of cell-type determination. These transcription factors are believed to activate the expression of cell-type-specific genes to generate stable differentiated cell types. The expression of bHLH proteins, in turn, is regulated by spatial cues, so that switches in cell type occur in a reproducible pattern. We report here that the lin-32 gene of Caenorhabditis elegans, which encodes a bHLH protein of the Drosophila achaete-scute family of transcription factors, is necessary and in some cells sufficient for specification of the neuroblast cell fate. Similarity in the function and structure of the lin-32 protein (LIN-32) to transcription factors of the achaete-scute gene family in Drosophila and vertebrates implies that this class of transcription factors functioned in a primitive ancestral form to specify neuronal cell fate, supporting the proposition that certain basic mechanisms of cell-type determination have been conserved through metazoan evolution.
Amino Acid Sequence↗
Variable cell positions and cell contacts underlie morphological evolution of the rays in the male tails of nematodes related to Caenorhabditis elegans.
As a first step toward understanding their mechanism of morphological evolution, we compare the morphology and development of the male genitalia in 10 species of Rhabditidae, the family of nematodes that includes Caenorhabditis elegans. We describe a number of variable morphological characteristics and focus in particular on the differing arrangements of the caudal papillae or rays within the acellular fan. We analyze the development of the ray cells within the epidermis of the last larval stage and identify changes in cell positions and cell contacts that underlie evolutionary changes in the arrangement of the rays. Epidermal cell positions were determined by means of indirect immunofluorescence staining with a monoclonal antibody directed towards adherens junctions. Similarities between the species in the cellular arrangements during the earliest developmental stages allow us to propose homologies between the rays in different species. Evolutionary changes in the positions and order of homologous rays are correlated with shifts in cell positions during development. The results suggest that genes for cell recognition or adhesion proteins, or pattern formation genes that regulate cell recognition or adhesion proteins, may be important foci of evolutionary change affecting morphology.
Animals↗
18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis.
We have investigated the molecular evolution of the nucleotide sequences of 18S ribosomal RNA genes (18S rDNA) from a set of nematodes in the family Rhabditidae (Nematoda: Secernentea). Our aim was to evaluate the usefulness of this gene for molecular systematics of this family, as well as to establish phylogenetic relationships within a group that has potential for comparative studies of the relationship between development and evolution. We determined the 18S rDNA sequences of nine species of nematodes representing six genera within this family (Caenorhabditis briggsae, C. vulgaris, C. remanei, Rhabditis blumi, Rhabditis sp. br, Rhabditella axei, Pellioditis typica. Teratorhabditis palmarum, and Pelodera strongyloides dermatitica). Using hypothetical models for secondary structure as well as nucleotide similarity, these sequences were aligned with the 18S rDNA sequence published by Ellis et al. for C. elegans and with the partial sequences published by Nadler for eight ascaridoid species. We find that 18S rDNA is likely to be a useful tool to resolve relationships at the intrafamilial level. However, 18S rDNA sequences cannot be used to resolve relationships between taxa as closely related as the Caenorhabditis species. Parsimony, minimum-evolution, and maximum-likelihood methods strongly reject Andrássy's proposed phylogenetic classification based on adult morphological characters but support that of Sudhaus as one alternative of a few possible phylogenies. Distances between genera in this family are about eight times as great as distances between tetrapod classes, suggesting rapid rates of substitution, ancient divergence, or both.
Animals↗
The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates.
The gene mab-21, which encodes a novel protein of 386 amino acids, is required for the choice of alternate cell fates by several cells in the C. elegans male tail. Three cells descended from the ray 6 precursor cell adopt fates of anterior homologs, and a fourth, lineally unrelated hypodermal cell is transformed into a neuroblast. The affected cells lie together in the lateral tail epidermis, suggesting that mab-21 acts as part of a short-range pattern-formation mechanism. Each of the changes in cell fate brought about by mab-21 mutants can be interpreted as a posterior-to-anterior homeotic transformation. mab-21 mutant males and hermaphrodites have additional pleiotropic phenotypes affecting movement, body shape and fecundity, indicating that mab-21 has functions outside the tail region of males. We show that the three known alleles of mab-21 are hypomorphs of a new gene. Mosaic analysis revealed that mab-21 acts cell autonomously to specify the properties of the sensory ray, but non-autonomously in the hypodermal versus neuroblast cell fate choice. Presence of cell signalling in the choice of the neuroblast fate was confirmed by cell ablation experiments. Mutations in mab-21 were shown previously to be genetic modifiers of the effects of HOM-C/Hox gene mutations on ray identity specification. The results presented here support the conclusion that mab-21 acts as part of a mechanism required for correct cell fate choice, possibly involving the function of HOM-C/Hox genes in several body regions.
Alleles↗
Widespread occurrence of the Tc1 transposon family: Tc1-like transposons from teleost fish.
We characterized five transposable elements from fish: one from zebrafish (Brachydanio rerio), one from rainbow trout (Salmo gairdneri), and three from Atlantic salmon (Salmo salar). All are closely similar in structure to the Tc1 transposon of the nematode Caenorhabditis elegans. A comparison of 17 Tc1-like transposons from species representing three phyla (nematodes, arthropods, and chordates) showed that these elements make up a highly conserved transposon family. Most are close to 1.7 kb in length, have inverted terminal repeats, have conserved terminal nucleotides, and each contains a single gene encoding similar polypeptides. The phylogenetic relationships of the transposons were reconstructed from the amino acid sequences of the conceptual proteins and from DNA sequences. The elements are highly diverged and have evidently inhibited the genomes of these diverse species for a long time. To account for the data, it is not necessary to invoke recent horizontal transmission.
Amino Acid Sequence↗
Selective lineage specification by mab-19 during Caenorhabditis elegans male peripheral sense organ development.
The action of the gene mab-19 is required for specification of a subset of Caenorhabditis elegans male peripheral sense organ (ray) lineages. Two mab-19 alleles, isolated in screens for ray developmental mutations, resulted in males that lacked the three most posterior rays. Cell lineage alterations of male-specific divisions of the most posterior lateral hypodermal (seam) blast cell, T, resulted in the ray loss phenotype in mab-19 mutant animals. Postembryonic seam lineage defects were limited to male-specific T descendent cell divisions. Embryonic lethality resulted when either mab-19 mutation was placed over a chromosomal deficiency encompassing the mab-19 locus. The earliest detectable defect was aberrant hypodermal cell movements during morphogenesis. From these data, it is inferred that both mab-19 alleles described are hypomorphs, and further reduction of mab-19 function results in embryos that are unable to complete morphogenesis. Thus, mab-19 may play a larger role in developmental regulation of hypodermal cell fate, including sensory ray development in males. Body morphology mutations, passage through the dauer stage, and heat or CdCl2 treatment suppressed mab-19 male phenotypes. A model is presented in which all three types of suppression result in a physiological stress response, which in turn leads to correction of the mab-19 defect.
Alleles↗
HOM-C/Hox genes and four interacting loci determine the morphogenetic properties of single cells in the nematode male tail.
The copulatory structure of the C. elegans male tail includes a set of nine bilaterally symmetrical pairs of sense organs known as rays. Each ray comprises three cells, which are generated by a stereotyped cell sublineage expressed by 18 epidermal ray precursor cells. A pattern formation mechanism in the epidermis guides the specification of morphogenetic differences between the rays necessary for correct organelle assembly at specific positions within the epidermis. Expression of these ray differences was altered in mutations we described previously, resulting in displaced and fused rays. Here we show that two genes of the C. elegans HOM-C/Hox gene complex play a role in the pattern formation mechanism. Increasing or decreasing the gene dosage of mab-5, an Antennapedia homolog, and egl-5, an Abdominal B homolog, results in displacement and fusion of specific rays. These changes are interpreted as anterior or posterior transformations in ray identities. Mutations in the genes previously described are dominant modifiers of these effects. This suggests that these genes act in the same morphogenetic pathway as mab-5 and egl-5. Several lines of evidence, including cell ablation experiments, argue that the identity of each ray is specified cell-autonomously in the terminal cells of the ray lineages. mab-5 and egl-5, therefore, specify the morphogenetic properties of differentiating cells, without change in cell lineage or apparent cell type. Modifier genes may act upstream of mab-5 and egl-5 to regulate their expression. Alternatively, they may act at the same step in the pathway, as cofactors, or they may be target genes. Target genes could include genes specifying cell recognition and adhesion molecules governing ray organelle assembly.
Animals↗
Extrachromosomal circular copies of the transposon Tc1.
The 1.6 kb Tc1 transposable element of Caenorhabditis elegans undergoes excision and transposition in the germline. In somatic tissue it is excised at high frequency. Extrachromosomal linear and circular copies of Tc1 have been identified that are likely to be products of somatic and germline excision. In the present study, we have determined the sequences of the sites of circularization in circular extrachromosomal Tc1 molecules. DNA molecules containing these sites were cloned after PCR amplification with primers directed outward from within Tc1. Sequences were obtained with two complete Tc1 ends and one or more intervening copies of the TA dinucleotide, with one complete end and one deleted end, and with two deleted ends. The 24 clones had different structures, indicating the pool of molecules serving as PCR templates was heterogeneous. The predominant circular junction had one or more nucleotides deleted from at least one transposon end. Such a molecule without two complete ends might not be expected to serve as a transposition intermediate. Hence, some extrachromosomal circular Tc1 molecules may result from a deadend excision pathway.
Animals↗
From cell fates to morphology: developmental genetics of the Caenorhabditis elegans male tail.
The C. elegans male tail is being studied as a model to understand how genes specify the form of multicellular animals. Morphogenesis of the specialized male copulatory organ takes place in the last larval stages during male development. Genetic analysis is facilitated because the structure is not necessary for male viability or for strain propagation. Analysis of developmental mutants, isolated in several functional and morphological screens, has begun to reveal how fates of cells are determined in the cell lineages, and how the specification of cell fates affects the morphology of the structure. Cytological studies in wild type and in mutants have been used to study the mechanism of pattern formation in the tail peripheral nervous system. The ultimate goal is to define the entire pathway leading to the male copulatory organ.
Animals↗
Continuous arterial pressure monitoring during magnetic resonance imaging--an alternative method.
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Humans↗