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C Kenyon

Publications and source records attributed to C Kenyon.

At least 37 records · Page 2Linked to original sources

Cell contact regulates neuroblast formation in the Caenorhabditis elegans lateral epidermis.

A single line of epidermal seam cells lies along each side of the nematode C. elegans. During normal development, one of these cells, V5, produces a neuroblast that will give rise to a sensory structure, the postdeirid. If seam cells located either anterior or posterior to V5 are ablated however, this neuroblast formation is blocked. Because of this requirement for the presence of adjacent seam cells, we have asked whether V5's ability to produce a neuroblast depends on direct contact with its seam cell neighbors. We find that direct contact between seam cells is required for commitment to neuroblast production. Seam cells lose and reform their contacts with each other as they go through rounds of cell division during larval development. Signaling required for neuroblast formation occurs when the seam cells make contact after their first round of division. If this contact is prevented, no neuroblast is made; when it is delayed, the time of signaling is also delayed. The characteristics of these signals suggest that a seam cell must be part of a continuous epithelium in order to develop normally and that signaling may occur via a cell recognition/cell adhesion pathway. The effect of seam cell ablations on neuroblast formation is altered in mab-5(-) animals, suggesting that this HOM-C gene is part of the pathway by which seam cell signaling controls the decision to make a postdeirid neuroblast.

Animals

A C. elegans mutant that lives twice as long as wild type.

We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.

Animals

A homeotic gene cluster patterns the anteroposterior body axis of C. elegans.

In insects and vertebrates, clusters of Antennapedia class homeobox (HOM-C) genes specify anteroposterior body pattern. The nematode C. elegans also contains a small cluster of HOM-C genes, one of which has been shown to specify positional identity. Here we show that two additional C. elegans HOM-C genes also specify positional identity and that together these three HOM-C genes function along the anteroposterior axis in the same order as their homologs in other organisms. Thus, HOM-C-based pattern formation has been conserved in nematodes despite the many differences in morphology and embryology that distinguish them from other phyla. Each C. elegans HOM-C gene is responsible for a distinct body region; however, where their domains overlap, two HOM-C genes can act together to specify the fates of individual cells.

Amino Acid Sequence

Multiple HOM-C gene interactions specify cell fates in the nematode central nervous system.

Intricate patterns of overlapping HOM-C gene expression along the A/P axis have been observed in many organisms; however, the significance of these patterns in establishing the ultimate fates of individual cells is not well understood. We have examined the expression of the Caenorhabditis elegans Antennapedia homolog mab-5 and its role in specifying cell fates in the posterior of the ventral nerve cord. We find that the pattern of fates specified by mab-5 not only depends on mab-5 expression but also on post-translational interactions with the neighboring HOM-C gene lin-39 and a second, inferred gene activity. Where mab-5 expression overlaps with lin-39 activity, they can interact in two different ways depending on the cell type: They can either effectively neutralize one another where they are both expressed or lin-39 can predominate over mab-5. As observed for Antennapedia in Drosophila, expression of mab-5 itself is repressed by the next most posterior HOM-C gene, egl-5. Thus, a surprising diversity in HOM-C regulatory mechanisms exists within a small set of cells even in a simple organism.

Animals

Two wnt genes in Caenorhabditis elegans.

wnt genes encode secretory glycoproteins that have been implicated in growth control and development in mice, frogs and insects. In this report we examine properties of two wnt genes recently identified in the nematode Caenorhabditis elegans. The first gene, Ce-wnt-1, was previously identified by a polymerase chain reaction-based screen of genomic DNA, and the second, Ce-wnt-2, was fortuitously encountered in a survey of clones in a cDNA library by the Caenorhabditis Genome Project. Full-length or nearly full-length cDNAs representing both mRNAs encode proteins that are similar in length, sequence and functional domains to other Wnt proteins. Primary products of 372 and 362 amino acids begin with a hydrophobic signal peptide, include two potential N-linked glycosylation sites and contain the 22 cysteine residues conserved throughout the wnt family. In contrast to mammalian and insect wnt genes with four or five exons and conserved intron-exon boundaries, Ce-wnt-1 has nine coding exons; only one of the eight identified introns interrupts the coding sequence at a position homologous to an intron position in other wnt genes. The major transcript derived from Ce-wnt-1 is 1.4 kb in length, and the 22 nucleotides at its 5' end are added by a trans-splicing mechanism. Ce-wnt-2 is also expressed via a single major transcript, 1.5 kb in length. Both RNAs are detectable in all larval forms and adults, but they are most abundant at the embryonic stage. Ce-wnt-1 is localized to the left arm of chromosome II and Ce-wnt-2 maps to a cluster of genes on chromosome IV.

Amino Acid Sequence

Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of migration.

Anterior-posterior patterning in insects, vertebrates and nematodes involves members of conserved Antennapedia-class homeobox gene clusters (HOM-C) that are thought to give specific body regions their identities. The effects of these genes on region-specific body structures have been described extensively, particularly in Drosophila, but little is known about how HOM-C genes affect the behaviours of cells that migrate into their domains of function. In Caenorhabditis elegans, the Antennapedia-like HOM-C gene mab-5 not only specifies postembryonic fates of cells in a posterior body region, but also influences the migration of mesodermal and neural cells that move through this region. Here we show that as one neuroblast migrates into this posterior region, it switches on mab-5 gene expression; mab-5 then acts as a developmental switch to control the migratory behaviour of the neuroblast descendants. HOM-C genes can therefore not only direct region-specific patterns of cell division and differentiation, but can also act within migrating cells to programme region-specific migratory behaviour.

Animals

Non-granulated peripolar cells exist in the rat glomerulus.

The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules.

Animals

Cell signals allow the expression of a pre-existent neural pattern in C. elegans.

In C. elegans, a simple pattern develops within a row of epidermal precursor cells, V1-V6. One cell, V5, gives rise to a neuroblast called the postdeirid neuroblast, while the other V cells produce epidermal cells instead. Here we describe experiments suggesting that in order for V5 to produce the postdeirid it must be in close or direct contact with neighboring V cells. Signaling between V cells is required for the formation of the neuroblast; however, which of the V cells can make a postdeirid is not determined by these signals but rather by the action of the homeotic lin-22 and pal-1 genes. These genes prevent V cells in specific body regions from responding to intercellular signals and producing postdeirids. This is a clear example of cell signals playing a permissive rather than an instructive role in neuroblast induction.

Animals

Expression of the homeotic gene mab-5 during Caenorhabditis elegans embryogenesis.

mab-5 is a member of a complex of homeobox-containing genes evolutionarily related to the Antennapedia and bithorax complexes of Drosophila melanogaster. Like the homeotic genes in Drosophila, mab-5 is required in a particular region along the anterior-posterior body axis, and acts during postembryonic development to give cells in this region their characteristic identities. We have used a mab-5-lacZ fusion integrated into the C. elegans genome to study the posterior-specific expression of mab-5 during embryogenesis. The mab-5-lacZ fusion was expressed in the posterior of the embryo by 180 minutes after the first cleavage, indicating that the mechanisms responsible for the position-specific expression of mab-5-lacZ act at a relatively early stage of embryogenesis. In embryos homozygous for mutations in the par genes, which disrupt segregation of factors during early cleavages, expression of mab-5-lacZ was no longer localized to the posterior. This suggests that posterior-specific expression of mab-5 depends on the appropriate segregation of developmental factors during early embryogenesis. After extrusion of any blastomere of the four-cell embryo, descendants of the remaining three cells could still express the mab-5-lacZ fusion. In these partial embryos, however, the fusion was often expressed in cells scattered throughout the embryo, suggesting that cell-cell interactions and/or proper positioning of early blastomeres are required for mab-5 expression to be localized to the posterior.

Animals

Regulation of cellular responsiveness to inductive signals in the developing C. elegans nervous system.

In Caenorhabditis elegans, cell-cell communication is required to form a simple pattern of sensory ray neurons and cuticular structures (alae). The C. elegans pal-1 gene initiates one developmental pathway (ray lineages) simply by blocking a cell-cell interaction that induces an alternative pathway. Here we show by mosaic analysis that pal-1+ acts by preventing specific cells from responding to inductive signals. The results indicate that although cell signals play a critical role in generating this pattern, they do not provide spatial information. Instead, signals are sent to many, if not all, of the precursor cells, and the ability to respond is spatially restricted. This patterning strategy thus differs from many well known models for pattern formation in which localized inductive signals influence a subset of cells within a field. We find that pal-1 encodes a homeodomain protein and so is likely to regulate transcription. The pal-1+ protein could block the response to cell signals either by repressing genes involved in signal transduction or by acting directly on downstream genes in a way that neutralizes the effects of the intercellular signals. Genetic experiments indicate that one candidate for such a downstream gene is the Antennapedia-like homeotic selector gene mab-5.

Amino Acid Sequence

Collateral branching innervation of rat molar teeth from trigeminal ganglion cells shown by double labelling with fluorescent retrograde tracers.

Somatotopic projections of each maxillary molar tooth were defined by injecting individual teeth with True blue and plotting the location of fluorescent cells in sections of the trigeminal ganglia. Collateral branching was investigated by injecting True blue and Diamidino yellow into pairs of maxillary molar teeth and examining the ganglia for double labelled cells. Maxillary molar teeth project to the lateral ophthalmomaxillary region of the ipsilateral ganglion with extensive overlap of the projections from individual teeth. Double labelling with both dyes demonstrated considerable collateral branching from single trigeminal ganglion cells to the molar teeth.

Animals

Selective silencing of cell communication influences anteroposterior pattern formation in C. elegans.

In C. elegans males, laterally located V cells generate a simple pattern of anterior alae (cuticular ridges) and posterior rays (mating sensilla). We have found that this pattern is generated, at least in part, by the selective interruption of cell-cell interactions. In anterior V cells, lineages leading to the production of alae are induced by cell interactions. These cell interactions are inhibited in specific posterior V cells by the activity of the gene pal-1, which allows these cells to generate rays instead of alae. The activities of cell signals and pal-1 appear to influence V cell fates by determining the state of a developmental switch that involves two homeotic genes, lin-22 and mab-5.

Alleles

Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification.

The study of gene family members has been aided by the isolation of related genes on the basis of DNA homology. We have adapted the polymerase chain reaction to screen animal genomes very rapidly and reliably for likely gene family members. Using conserved amino acid sequences to design degenerate oligonucleotide primers, we have shown that the genome of the nematode Caenorhabditis elegans contains sequences homologous to many Drosophila genes involved in pattern formation, including the segment polarity gene wingless (vertebrate int-1), and homeobox sequences characteristic of the Antennapedia, engrailed, and paired families. In addition, we have used this method to show that C. elegans contains at least five different sequences homologous to genes in the tyrosine kinase family. Lastly, we have isolated six potassium channel sequences from humans, a result that validates the utility of the method with large genomes and suggests that human potassium channel gene diversity may be extensive.

Amino Acid Sequence

Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox.

During postembryonic development in C. elegans, posterior-specific pattern formation requires the gene mab-5. Within the posterior body region, mab-5 activity controls epidermal, neuronal, and mesodermal cell differentiation, and also the direction of cell migration. Here, we show that mab-5 RNA is localized in the posterior body region, indicating that mab-5 activity is targeted to posterior cells, at least in part, by a mechanism that operates at the level of mab-5 RNA synthesis or stabilization. We also show that mab-5 contains a homeobox similar to that of the Drosophila Antennapedia gene. This suggests that mab-5 influences cell differentiation and cell migration by regulating gene expression, and clearly demonstrates that genes containing homeoboxes influence global aspects of pattern formation in organisms other than Drosophila.

Amino Acid Sequence

The nematode Caenorhabditis elegans.

In Caenorhabditis elegans patterns of cell division, differentiation, and morphogenesis can be observed with single-cell resolution in intact, living animals. Mechanisms that determine behaviors of individual cells during development are being dissected by means of genetic, cell biological, and molecular approaches.

Animals

A gene involved in the development of the posterior body region of C. elegans.

Many regional differences in Caenorhabditis elegans body pattern are generated after hatching. Here I describe a gene, mab-5, that is required for the postembryonic development of nearly all ectodermal and mesodermal features that normally characterize a posterior body region. In addition, this gene is necessary for most cell migrations toward the posterior, but not for cell migrations toward the anterior. mab-5+ activity is cell-autonomous. In animals carrying a mutation in the gene lin-22, increases or decreases in mab-5+ gene dosage produce corresponding increases or decreases in the size of the region in which cells adopt posterior-specific fates. The model that best explains the data is that during postembryonic development, posterior-specific patterns of cell differentiation and cell migration are initiated by graded positional information, and that a common step in the different cellular responses to this information is mediated by mab-5 activity.

Animals