Zeng XS et al. (2018) ASN Neuro "Neurotoxin-Induced Animal Models of Parkinson Disease: Pathogenic Mechanism and Assessment."

Jia JJ, Geng WS, Zeng XS

[ASN Neuro, 2018]

Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies. In this review, we will highlight the pathogenic mechanisms of those neurotoxins and summarize different neurotoxic animal models with the hope to help researchers choose among them accurately and to promote the development of modeling PD.

Sharma R et al. (2014) Genes Dev "Differential spatial and structural organization of the X chromosome underlies dosage compensation in C. elegans."

Kind J, Vaillant C, Meister P, Jost D, Askjaer P, Sharma R, Gomez-Saldivar G, van Steensel B

[Genes Dev, 2014]

The adjustment of X-linked gene expression to the X chromosome copy number (dosage compensation [DC]) has been widely studied as a model of chromosome-wide gene regulation. In Caenorhabditis elegans, DC is achieved by twofold down-regulation of gene expression from both Xs in hermaphrodites. We show that in males, the single X chromosome interacts with nuclear pore proteins, while in hermaphrodites, the DC complex (DCC) impairs this interaction and alters X localization. Our results put forward a structural model of DC in which X-specific sequences locate the X chromosome in transcriptionally active domains in males, while the DCC prevents this in hermaphrodites.

Fong Y et al. (2002) Science "Regulation of the different chromatin states of autosomes and X chromosomes in the germ line of C. elegans."

Strome S, Fong Y, Bender L, Wang W

[Science, 2002]

The Maternal-Effect Sterile (MES) proteins are essential for germline viability in Caenorhabditis elegans. Here, we report that MES-4, a SET-domain protein, binds to the autosomes but not to the X chromosomes. MES-2, MES-3, and MES-6 are required to exclude MES-4 and markers of active chromatin from the X chromosomes. These findings strengthen the emerging view that in the C. elegans germ line, the X chromosomes differ in chromatin state from the autosomes and are generally silenced. We propose that all four MES proteins participate in X-chromosome silencing, and that the role of MES-4 is to exclude repressors from the autosomes, thus enabling efficient repression of the Xs.

Segalat LS et al. (1995) Science "Modulation of serotonin-controlled behaviors by Go in Caenorhabditis elegans."

Segalat LS, Elkes DA, Kaplan JM

[Science, 1995]

Seven transmembrane receptors and their associated heterotrimeric guanine nucleotide-binding proteins (G proteins) have been proposed to play a key role in modulating the activities of neurons and muscles. The physiological function of the Caenorhabditis elegans G protein G(o) has been genetically characterized. Mutations in the goa-l gene, which encodes an a subunit of G(o) (G alpha(o)), cause behavioral defects similar to those observed in mutants that lack the neurotransmitter serotonin (5-HT), and goa-1 mutants are partially resistant to exogenous 5-HT. Mutant animals that lack G alpha(o) and transgenic animals that overexpress G alpha(o) [goa-l(xs) animals] have reciprocal defects in locomotion, feeding, and egg laying behaviors. In normal animals, all of these behaviors are regulated by 5-HT. These results demonstrate that the level of G(o) activity is a critical determinant of several C. elegans behaviors and suggest that G(o) mediates many of the behavioral effects of 5-HT.

Anderson EC et al. (2019) Dev Cell "X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation."

Yang Q, Meyer BJ, Bian Q, Podshivalova K, Anderson EC, Higuchi-Sanabria R, Frankino PA, Kenyon C, Shin A, Dillin A

[Dev Cell, 2019]

Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-sized topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundaries. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating that a rex site is necessary and sufficient to define DCC-dependent boundary locations. Deleting eight rex sites (8rex) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rex animals exhibited no changes inXexpression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor the consequence of DCC-mediated gene repression. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in stress responses and aging.