Chen, Shang-Yang et al. (2017) International Worm Meeting "Regulation of male meiotic divisions in C. elegans."

Wu, Jui-Ching, Lin, Yi-Shiu, Chen, Shang-Yang

[International Worm Meeting, 2017]

Different from mitotic cells, spermatocytes and oocytes divide twice after one round of chromosome duplication. Therefore, it is intriguing whether the two divisions are regulated by the same principles as in mitosis. Using time-lapse recording, we followed the kinetics of chromosome-associated division regulators during male meiotic divisions. We found that while inner kinetochore persists throughout the two divisions, outer kinetochore is released from chromosomes during first chromosome segregation event and recruited back before second division. This suggests that a functional kinetochore is disassembled and then re-assembled between first and second divisions. Because the kinetochore also plays essential roles in spindle assembly checkpoint (SAC), we examined if a functional checkpoint is also re-established after first division. Interestingly, securin, the downstream target of SAC, though is degraded during first chromosome separation, is not recruited back to chromosome for the second division. These results suggest the second male meiotic division is not controlled through timely degradation of securin, which is dependent on APC/C and proteasome. Consistent with this, temperature-sensitive APC/C mutant adult males do not show accumulation of arrested secondary spermatocytes when shifted to non-permissive temperature. To further explore how the two division events are regulated differently, we examined localization of Aurora B kinase in dividing spermatocytes. During first division, Aurora B kinase is specifically localized in between homologous but not sister chromosomes. This localization pattern is dependent on PP1 phosphatase GSP-2: Aurora B kinase spreads to sister chromosomes in the absence of GSP-2. Consistent with Aurora B kinase promotes cohesion removal, gsp-2 mutant spermatocytes exhibit premature sister chromatid separation. These results support that during first meiotic division GSP-2 protects sister cohesion from being degraded by separase, which is regulated through the SAC signals. Taken together, we hypothesize that the two male meiotic divisions are regulated through different mechanisms. The first division is regulated by canonical SAC signaling and dependent on APC/C activity. Contrarily, the second division is independent of APC-proteasome activity. Initiation of chromosome separation in second division might rely on release of sister cohesion that is protected from degradation during first division by PP1 phosphatases GSP-2.

Chen, Shang-Yang et al. (2019) International Worm Meeting "Male meiotic chromosome segregation is not subjected to rigorous checkpoint regulation."

Chen, Shang-Yang, Wu, Jui-Ching

[International Worm Meeting, 2019]

During male meiosis, the duplicated chromosomes undergo two consecutive separation events. Because chromosome segregation is strictly regulated by the spindle assembly checkpoint (SAC), we asked whether both male meiotic divisions are also regulated by the same principle. Although outer kinetochore BUB-1, acting as SAC signaling platform, is disassembled and reassembled between two divisions, we found the SAC target securin is degraded during first division and remained undetectable through the second division. Interestingly, though administration of proteasome inhibitor arrested primary spermatocytes at anaphase I, division of secondary spermatocytes was not affected by inhibition of proteasome. These results show that SAC-dependent protein degradation does not play role in the second male meiotic chromosome segregation. To test whether SAC is indeed dispensable from second male meiotic division, we examined the division of primary and secondary spermatocytes with monopolar spindle. Surprisingly, monopolar spindle only minimally delayed both divisions, with timely disassembly of the outer kinetochore. Additionally, SAC-defective mutant mdf-1 did not show significant effect in monopolar primary and secondary spermatocytes. Furthermore, spermatocytes with defective spindle would skip division and proceed to final stage that generates abnormal spermatids. Taken together, our results show that the male meiotic chromosome segregation is not subjected to rigorous checkpoint control.

(2017) Toxicol Sci "4-Bromodiphenyl Ether Induces Germ Cell Apoptosis by Induction of ROS and DNA Damage in Caenorhabditis elegans."

[Toxicol Sci, 2017]

The corresponding authorship has been updated to reflect Yang Luan and Jinfu Zhango as co-corresponding authors in the final version.

Fechner S et al. (2018) MicroPubl Biol "The bodies of dpy-10(e128) are twice as stiff as wild type"

Loizeau F, Pruitt B, Nekimken AL, Goodman MB, Fechner S

[MicroPubl Biol, 2018]

DPY-10 is a collagen protein in the nematodes cuticle. Mutations in the dpy-10 gene induce various morphological changes that lead to animals with a dumpy (Dpy) or roller (Rol) phenotype (Levy, Yang and Kramer, 1993).

Po MD et al. (2012) Neuron "Releasing the inner inhibition for axon regeneration."

Po MD, Calarco JA, Zhen M

[Neuron, 2012]

The adult mammalian central nervous system exhibits restricted regenerative potential. Chen etal. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.

Silverstein NJ et al. (2017) Immunity "Interleukin-17: Why the Worms Squirm."

Huh JR, Silverstein NJ

[Immunity, 2017]

IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen etal. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.

Ahmad W et al. (2020) Biochem Biophys Res Commun "Prediction of human tau 3D structure, and interplay between O--GlcNAc and phosphorylation modifications in Alzheimer's disease: C.elegans as a suitable model to study these interactions invivo."

Ahmad I, Ahmad W, Shabbiri K

[Biochem Biophys Res Commun, 2020]

Tau protein regulates, maintains and stabilizes microtubule assembly under normal physiological conditions. In certain pathological circumstances, tau is post-translationally modified predominantly via phosphorylation and glycosylation. Hyper-phosphorylation of tau in Alzheimer's disease (AD) resulted in aggregated neurofibrillary tangles (NFTs) formation. Unfortunately, absence of tau 3D structure makes difficult to understand exact mechanism involved in tau pathology. Here by using ab-initio modelling, we predicted a tau 3D structure that not only explains its binding with microtubules but also elucidates NFTs formation. O-linked -N-acetylglucosaminylation (O--GlcNAc) is thought to regulate tau phosphorylation on single or proximal Ser/Thr residues (called as Yin-Yang sites). In this study, we not only validate the previously described three-serine residues (208, 238 and 400) as Yin-Yang sites but also predicted 22 more possible Ser/Thr O-glycosylation sites. Among them seventeen residues were predicted as possible Yin-Yang sites and are proposed to mediate NFT formation in AD. These predicted Yin-Yang sites may act as attractive therapeutic targets for the drug development in AD. Predicted 3D structure of tau₄₄₁ was highly accessible for phosphorylation and hyperphosphorylation, and showed higher surface accessibility for interplay between O--GlcNAc and phosphorylation modifications. Kinases and phosphatases involved in tau phosphorylation are conserved in human and other organisms. Homology modelling revealed conserved catalytic domain for both human and C.elegans O-GlcNAc transferase (OGT), suggesting that transgenic C.elegans expressing human tau may be a suitable model system to study these modifications.

Artan M et al. (2016) Dev Cell "Heat FLiPs a Hormonal Switch for Longevity."

Lee SV, An SW, Artan M

[Dev Cell, 2016]

Temperature-sensing neurons in C.elegans reduce the life-shortening effects of high temperatures via steroid signaling. In this issue of Developmental Cell, Chen etal. (2016) elucidate the underlying mechanisms by which the transcription factor CREB induces the neuropeptide FLP-6 in the temperature-sensing neurons to counteract the life-shortening effects of high temperature.

Akin O et al. (2014) Cell "The shape of things to come."

Akin O, Zipursky SL

[Cell, 2014]

Surface receptors can link binding of ligands to changes in the actin-based cell cytoskeleton. Chia etal. and Chen etal. provide evidence for direct binding between the cytoplasmic tails ofreceptorsand the WAVE complex, a regulator of the actin nucleator Arp2/3 complex, which mighthelp to explain how environmental signals are translated into changes in morphology andmotility.

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan