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M Driscoll

Publications and source records attributed to M Driscoll.

48 records · Page 3Linked to original sources
PubMed1993

Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans.

Six touch receptor neurons with distinctive morphological features sense gentle touch in Caenorhabditis elegans. Previous studies have identified three genes (lin-32, unc-86 and mec-3) that regulate touch cell development. However, since other cell types also require these genes, we suspected that other genes help restrict the expression of touch cell characteristics to the six neurons seen in the wild type. To identify such genes, we have examined mutants defective in genes required for the development of other C. elegans cells for changes in the pattern of touch cell-specific features. Mutations in seven genes either reduce (lin-14) or increase (lin-4, egl-44, egl-46, sem-4, ced-3 and ced-4) the number of touch receptor-like cells. The combinatorial action of these genes, all of which are required for the production of many cell types, restrict the number of cells expressing touch receptor characteristics in wild-type animals by acting as positive and negative regulators and by removing cells by programmed cell death.

Animals↗
PubMed1992

Molecular genetics of cell death in the nematode Caenorhabditis elegans.

In C. elegans, cell death can be readily studied at the cellular, genetic, and molecular levels. Two types of death have been characterized in this nematode: (1) programmed cell death, which occurs as a normal component in development; and (2) pathological cell death, which occurs aberrantly as a consequence of mutation. Analysis of mutations that disrupt programmed cell death in various ways has defined a genetic pathway for programmed cell death which includes genes that perform such functions as the determination of which cells die, the execution of cell death, the engulfment of cell corpses, and the digestion of DNA from dead cells. Molecular analysis is providing insight into the nature of the molecules that function in these aspects of programmed cell death. Characterization of some genes that mutate to induce abnormal cell death has defined a novel gene family called degenerins that encode putative membrane proteins. Dominant alleles of at least two degenerin genes, mec-4 and deg-1, can cause cellular swelling and late onset neurodegeneration of specific groups of cells.

Animals↗
PubMed1992

Developmental and abnormal cell death in C. elegans.

Genetic analysis in Caenorhabditis elegans has identified several genes that function in normal developmental death as well as genes that can mutate to cause inappropriate cell death. The processes whereby some of these abnormal deaths occur depend on genes that participate in normal programmed cell death; others occur by an independent mechanism whereby mutation of members of a gene family leads to cell lysis. Molecular characterization of these 'death' genes in C. elegans is beginning to provide insight into the normal and aberrant mechanisms of cell death.

Animals↗
PubMed1991

The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration.

Three dominant mutations of mec-4, a gene needed for mechanosensation, cause the touch-receptor neurons of Caenorhabditis elegans to degenerate. With deg-1, another C. elegans gene that can mutate to induce neuronal degeneration and that is similar in sequence, mec-4 defines a new gene family. Cross-hybridizing sequences are detectable in other species, raising the possibility that degenerative conditions in other organisms may be caused by mutations in similar genes. All three dominant mec-4 mutations affect the same amino acid. Effects of amino-acid substitutions at this position suggest that steric hindrance may induce the degenerative state.

Amino Acid Sequence↗
PubMed1991

Regional perinatal care in crisis: a case study of an urban public hospital.

Regionalized perinatal care is intended to guarantee pregnant women and neonates access to appropriate care regardless of ability to pay. Its effectiveness depends on the willingness of hospitals to transfer high-risk patients according to established protocols and affiliations. This study examines maternal transfers (n = 896) to Cook County Hospital (CCH), a public facility and a designated perinatal center in Chicago. In 1987 and 1988, the majority (68%) of maternal transfers to CCH came from out-of-network hospitals, and 52% of these came directly from another perinatal center. The data indicate that 62% of the out-of-network transfers who delivered were medically high-risk. The study also documents the transfer of women in active labor, a violation of federal law. The term "perinatal dumping" is introduced to mean the transfer of high-risk pregnant women between hospitals for economic rather than medical reasons. Strategies for safeguarding the integrity of regionalized perinatal care are discussed.

Adolescent↗
PubMed1989

Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity.

Benzimidazole anti-microtubule drugs, such as benomyl, induce paralysis and slow the growth of the nematode Caenorhabditis elegans. We have identified 28 mutations in C. elegans that confer resistance to benzimidazoles. All resistant mutations map to a single locus, ben-1. Virtually all these mutations are genetically dominant. Molecular cloning and DNA sequence analysis established that ben-1 encodes a beta-tubulin. Some resistant mutants are completely deleted for the ben-1 gene. Since the deletion strains appear to be fully resistant to the drugs, the ben-1 product appears to be the only benzimidazole-sensitive beta-tubulin in C. elegans. Furthermore, since animals lacking ben-1 are viable and coordinated, the ben-1 beta-tubulin appears to be nonessential for growth and movement. The ben-1 function is likely to be redundant in the nematode genome.

Alleles↗
PubMed1988

ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance.

In Saccharomyces cerevisiae, 3-amino-1,2,4-triazole (aminotriazole) competitively inhibits the activity of imidazoleglycerolphosphate dehydratase, the product of the HIS3 gene. Wild-type strains are able to grow in the presence of 10 mM aminotriazole because they induce the level of imidazoleglycerolphosphate dehydratase. However, strains containing gcn4 mutations are unable to grow in medium containing aminotriazole because they lack the GCN4 transcriptional activator protein necessary for the coordinate induction of HIS3 and other amino acid biosynthetic genes. Here, we isolated a new gene, designated ATR1, which when present in multiple copies per cell allowed gcn4 mutant strains to grow in the presence of aminotriazole. In wild-type strains, multiple copies of ATR1 permitted growth at extremely high concentrations of aminotriazole (80 mM), whereas a chromosomal deletion of ATR1 caused growth inhibition at very low concentrations (5 mM). When radioactive aminotriazole was added exogenously, cells with multiple copies of ATR1 accumulated less aminotriazole than wild-type cells, whereas cells with the atr1 deletion mutation retained more aminotriazole. Unlike the mammalian mdr or yeast PDR genes that confer resistance to many drugs, ATR1 appears to confer resistance only to aminotriazole. Genetic analysis, mRNA mapping, and DNA sequencing revealed that (i) the primary translation product of ATR1 contains 547 amino acids, (ii) ATR1 transcription is induced by aminotriazole, and (iii) the ATR1 promoter region contains a binding site for the GCN4 activator protein. The deduced amino acid sequence suggests that ATR1 protein is very hydrophobic with many membrane-spanning regions, has several potential glycosylation sites, and may contain an ATP-binding site. We suggest that ATR1 encodes a membrane-associated component of the machinery responsible for pumping aminotriazole (and possibly other toxic compounds) out of the cell.

Amino Acid Sequence↗
PubMedDate not supplied

Neural development. FESN Study Group.

The FESN-sponsored follow-up meeting on neural development highlighted progress toward understanding several central issues in developmental neurobiology with particular emphasis on investigation into the mechanisms of cell fate determination. In systems as diverse as the HSN neurons of C. elegans, the photoreceptor cells of the Drosophila eye, the wide range of cell types within the vertebrate retina and the neurons of the cerebral cortex, hindbrain and spinal cord, the importance of environment in the determination and maintenance of cell fate was clearly established. Advances in cell marking techniques, including fluorescent dye and retroviral tagging, have enabled the fates of cells in normal and heterotypic environments to be followed and have demonstrated the initial plasticity of the progenitor cell population in many systems. The recent establishment of in vitro systems for studying neural development should further define the precise nature and identity of the environmental signals that act to establish and maintain cell fate. Of course, establishment of cell identity is only the initial phase in the formation of the mature nervous system. Once the fate of individual cells is determined, migration of cells to appropriate locations, extension of axons to appropriate targets and refinement of neuronal circuitry must occur. Both the definition of genes that influence these processes in nematodes and recent advances in imaging techniques that provide a means of observing these later, dynamic processes in 'living' brain slices promise to significantly advance understanding of the complexities of development of functional nervous systems.

Animals↗