Link C et al. (1981) International C. elegans Meeting "age pigments of C elegans: quantitation and physical properties."

Jacobson LA, Russell RL, Link C

[International C. elegans Meeting, 1981]

Bi, Yu et al. (2015) International Worm Meeting "Preferential misregulation of spermatogenesis genes in male sterile C. nigoni carrying an X-linked C. briggsae fragment."

Xie, Dongying, Bi, Yu, Li, Runsheng, Zhao, Zhongying, Yan, Cheung, Shao, Jiaofang, Ren, Xiaoliang

[International Worm Meeting, 2015]

Genetic basis of hybrid incompatibility (HI), a collective term of compromised fitness in hybrid, including sterility and lethality, has been intensively studied in Drosophila species, but remains poorly understood in other species, especially in nematodes. Recent discovery of a C. briggsae sister species, C. nigoni, has opened up the possibility of dissecting the genetic basis of HI in nematode species. We have generated 96 chromosomally integrated GFP markers in the C. briggsae genome and mapped them into the defined locations by PCR and Next-Generation Sequencing (NGS). Aided by the marker, we backcrossed the GFP-associated C. briggsae genomic fragments into C. nigoni for at least 15 generations and produced 111 independent introgression lines. The introgression fragments cover most of the C. briggsae genome. We finally dissected the patterns of HI by scoring the embryonic lethality, larval arrest, sex ratio and male sterility for each introgression line, through which we identified pervasive HI loci and produced a genome-wide landscape of HI between the two nematode species, the first of its type for any non-Drosophila species.To further understand the genetic basis of HI between the two species, we focused on the molecular understanding of two introgression fragments that produce male sterility but are located on different parts of X chromosome. To this end, we performed RNA-seq for both sterile and parental males and quantified the reads using C. briggsae genome as a reference. A total of 957 genes were found differentially expressed (Fold Change>1.5, FDR<0.05) in both hybrids compared with both parental species with most genes showing down-regulation. Surprisingly, 364 out of 957 genes are those enriched during spermatogenesis, suggesting that preferential down-regulation of spermatogenesis genes caused by the introgression may at least partially to be blamed for the observed sterility. More details on the differentially expressed genes will be presented in the meeting.

Aamodt EJ et al. (1987) International C. elegans Meeting "microtubule cross-linking protein from C elegans."

Aamodt EJ, Culotti JG, Holmgren R

[International C. elegans Meeting, 1987]

Link CD (1993) International C. elegans Meeting "Transgenic approaches to amyloid disease cytopathology."

Link CD

[International C. elegans Meeting, 1993]

Link CD (1989) International C. elegans Meeting "C elegans mutants that ectopically bind wheat-germ agglutinin."

Link CD

[International C. elegans Meeting, 1989]

Wolfgang Link et al. (2001) International C. elegans Meeting "A transgenic C. elegans model for Parkinsons Disease"

Marius C Hoener, Wolfgang Link, Ralf Baumeister, Karlheinz Tovar

[International C. elegans Meeting, 2001]

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with resting tremor, muscle rigidity, bradykinesia and postural instability as primary diagnostic signs. The movement dysfunction results from specific degeneration of dopaminergic neurons in the substantia nigra. The neuropathological hallmark of PD is the Lewy body, a cytoplasmic inclusion largely composed of fibrils formed by the polymerized, presynaptic protein alpha-synuclein. The point mutations A53T and A30P in the alpha-synuclein gene are linked to an autosomal dominant form of familial PD suggesting that a toxic gain of function may participate in the pathophysiology of PD. As C. elegans has shown to be a powerful model organism for the study of human neurological diseases like Alzheimer's Disease and Huntington's Disease, we established a nematode model for PD based on the expression of human alpha-synuclein. We generated worms carrying extrachromosomal and integrated arrays of human wildtype and mutant alpha-synuclein controlled by the C. elegans promoters unc-119 and sel-12 . Transgenic worms containing constructs expressing alpha-synuclein in neurons produce axonal deposits with strong anti alpha-synuclein immunoreactivity implying transport to the presynapse and aggregation in the axon. Furthermore, we detected a high molecular alpha-synuclein aggregate that migrated in the stacking gel in immunoblotted worm protein extracts. Transgenic C. elegans expressing human alpha-synuclein display noticeable phenotypes including locomotor dysfunction, egg laying defect and morphological abnormalities suggesting alpha-synuclein toxicity. As it has been reported for the Drosophila model of PD we did not detect major phenotypic differences between worms containing wild type or mutant alpha-synuclein. Experiments to determine the fate of the dopaminergic neurons and the structure of alpha-synuclein deposits in the transgenic animals are in progress. In summary, we have created a transgenic model of PD that replicates key features of PD pathology.

CD Link et al. (1999) International C. elegans Meeting "Genetic analysis of beta amyloid toxicity in transgenic C. elegans"

CJ Johnson, A Fluet, CD Link, A Smith

[International C. elegans Meeting, 1999]

The beta amyloid peptide (Abeta) forms deposits in the brains of Alzheimer's disease patients and is believed to be central to the pathology of this disease. We have generated transgenic C. elegans animals expressing relatively high levels of human Abeta in hopes of modeling some aspects of this disease. Animals with muscle-specific expression of Abeta have amyloid deposits and show a distinctive, temperature-dependent progressive paralysis. Our recent studies suggest that this phenotype is a result of specific Abeta toxicity, and not due to non-specific effects of foreign protein expression or toxic properties of the transgenic array itself (e.g., titration of muscle-specific transcription factors). Specifically, we find that transgenic lines expressing equivalent or higher levels of the putative non-toxic met35cys or single chain dimer Abeta variants do not show the progressive paralysis. In addition, RNA inhibition of transgenic (wild-type) Abeta expression also completely blocks the paralysis phenotype. We have therefore undertaken initial screens to identify mutations that block Abeta toxicity, in order to identify genes involved in this process. From our initial small-scale screens, we have identified four mutations that significantly reduce the paralysis phenotype in transgenic animals. One extragenic mutant, dv54 , dramatically reduces transgene expression, and though intriguing, is presumably not relevant to Abeta toxicity. However, the other three mutants, dv53,55 , and 56 , express Abeta at parental levels and have amyloid deposits, yet still show suppression of the paralysis phenotype. These mutants are being further characterized. In collaboration with Stuart Kim, we are complementing this genetic analysis by examining gene expression profiles in amyloid and control animals using microarray hybridization.

Link CD et al. (1985) International C. elegans Meeting "looking for transposons in P redivivus."

Graf-Whitsel J, Wood WB, Link CD

[International C. elegans Meeting, 1985]

Link CD et al. (1987) International C. elegans Meeting "approaches to studying male tail morphogenesis."

Wood WB, Link CD

[International C. elegans Meeting, 1987]

Link CD et al. (1991) International C. elegans Meeting "Analysis of Pleiotropic Lectin-binding Mutants."

Silverman MA, Enyeart M, Breen M, Watt KE, Link CD

[International C. elegans Meeting, 1991]

We have identified mutations in three genes (srf-4, srf-8, and srf-9) that result in an unusual suite of pleiotropic defects: these mutants all ectopically bind lectins, are Unc, Mab, and progressive Egl, have SDSsensitive dauers and abnormal distal tip cell migration, and show strong enhancement of dominant I i n - 12 alleles . This motley spectrum of phenotypes cannot easily be explained solely as the result of a cuticle defect. We hypothesize that these mutants have an underlying hypodermal defect that affects the secretion of both the cuticle and the basal lamina (or other extracellular proteins). Because mutants in these three genes have such similar complex phenotypes, we believe these genes are involved in the same biological process, perhaps in different steps of the same pathway. One interesting posibility is that these mutants have an underlying defect in protein glycosylation. Consistent with this idea, these mutants have an altered pattern of cuticle glycoproteins on SDS gels. In an alternative approach, we have attempted to directly identify glycosylation mutants by isolating non-lectin-binding revertants of ( non-pleiotropic) srf mutants.