Biology subjects

Nishiwaki, K.

Publications and source records attributed to Nishiwaki, K..

6 recordsLinked to original sources

bioRxiv2025

The Greenland shark genome: insights into deep-sea ecology and lifespan extremes

The Greenland shark (Somniosus microcephalus) is known for its slow metabolism and deep-sea habitat. It is considered the longest-lived vertebrate on Earth, with an estimated lifespan of 392{+/-}120 years. Despite its remarkable longevity and lifestyle, there have been no genomic studies on this species. Here, we report the first, chromosome-level assembly of the Greenland shark genome, which is 5.9 Gb in size with an N50 length of 233 Mb, and contains 37,125 predicted genes with a completeness score of 86.5%. We found that the copy numbers of three gene families (TNF, TLR, LRRFIP), which are involved in activating the NF-{kappa}B signaling pathway, are significantly increased in the Greenland shark compared to short-lived shark species. In the rhodopsin of this deep-sea dweller, we detected amino acid substitutions that result in spectral tuning for the so-called blue shift, suggesting adaptive evolution to dim-light vision. We also elucidate the dynamics of the effective population size (Ne) of the Greenland shark and its close relative, the Pacific sleeper shark (Somniosus pacificus). These genomic analyses offer new insights into the molecular basis of the exceptional longevity of the Greenland shark and highlight potential genetic mechanisms that could inform future research into longevity.

genomics↗

bioRxiv2023

Ribosomal protein mutation suppresses gonadal leader cell migration defects in mig-17/ADAMTS mutants in Caenorhabditis elegans

The migration of the gonadal distal tip cells (DTCs) in Caenorhabditis elegans provides an excellent model for studying the migration of epithelial tubes during organogenesis. Mutations in the mig-17/ADAMTS gene cause misdirected migration of DTCs during gonad formation, resulting in deformed gonad arms. An amino-acid substitution in RPL- 20 corresponding to the mammalian RPL18a/eL20, a component of the 60S ribosomal large subunit, showed a slow growth phenotype and strongly suppressed the mig-17 gonadal defects. Slow-growing mutants clk-1 and clk-2 also suppressed mig-17, although weaker than rlp-20 mutants. MIG-17 recruits FBL-1C/fibulin-1C to the gonadal basement membrane to regulate DTC migration. Reducing the gene dosage of fbl-1 by half partially compromised the suppressor activity of the mutant rpl-20 gene on mig-17. Analysis using the mNeonGreen-FBL-1 reporter revealed that its localization to the gonadal basement membrane was significantly reduced in mig-17, whereas it was recovered to the wild-type levels in mig-17; rpl-20 double mutants. These results indicate that the rpl-20 mutation suppresses mig-17 gonadal defects through dual mechanisms: deceleration of growth rate and enhancement of FBL-1C recruitment to the gonadal basement membrane.

developmental biology↗

bioRxiv2021

Early Dynamics of Chronic Myeloid Leukemia on Nilotinib Predicts Deep Molecular Response

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase1,2. ABL1-selective tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML3-7. The ultimate goal of CML treatment is likely to be TKI-free maintenance of deep molecular response (DMR), which is defined by quantitative measurement of BCR-ABL1 transcripts on the international scale (IS)8, and durable DMR is a prerequisite to reach this goal9. Thus, an algorithm to enable the early prediction of DMR achievement on TKI therapy is quite valuable. Here, we show that our mathematical framework based on a clinical trial dataset10 can accurately predict the response to frontline nilotinib. We found that our simple dynamical model can predict nilotinib response by using two common laboratory findings (observation values): IS11,12 and white blood cell (WBC) count. Furthermore, our proposed method identified patients who failed to achieve DMR with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs in clinical practice. Significance StatementChronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. The goal of this treatment is the sequential achievement of deep molecular response (DMR). Tyrosine kinase inhibitors (TKIs) are effective in the reduction because they inhibit CML cell proliferation. However, because of individual differences in the TKI efficacy, some patients are unable to achieve DMR, so that early prediction of DMR reachability is necessary for personalized medicine. By combining time series analysis and mathematical modeling, we developed a mathematical method that accurately predicts patients who do not achieve DMR in the early stages of TKI administration. Our prediction method gives a basis of effective personalized treatments for CML patients.

systems biology↗

bioRxiv2020

Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans

During development of the Caenorhabditis elegans gonad, the gonadal leader cells, called distal tip cells (DTCs), migrate in a U-shaped pattern to form the U-shaped gonad arms. The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family metalloproteases MIG-17 and GON-1 are required for correct DTC migration. Mutations in mig-17 result in misshapen gonads due to the misdirected DTC migration, and mutations in gon-1 result in shortened and swollen gonads due to the premature termination of DTC migration. Although the phenotypes shown by mig-17 and gon-1 mutants are very different from one another, mutations that result in amino acid substitutions in the same basement membrane protein genes, emb-9/collagen IV a1, let-2/collagen IV a2 and fbl-1/fibulin-1, were identified as genetic suppressors of mig-17 and gon-1 mutants. To understand the roles shared by these two proteases, we examined the effects of the mig-17 suppressors on gon-1 and the effects of the gon-1 suppressors and enhancers on mig-17 gonadal defects. Some of the emb-9, let-2 and fbl-1 mutations suppressed both mig-17 and gon-1, whereas others acted only on mig-17 or gon-1. These results suggest that mig-17 and gon-1 have their specific functions as well as functions commonly shared between them for gonad formation. The levels of collagen IV accumulation in the DTC basement membrane were significantly higher in the gon-1 mutants as compared with wild type and were reduced to the wild-type levels when combined with suppressor mutations, but not with enhancer mutations, suggesting that the ability to reduce collagen IV levels is important for gon-1 suppression.

developmental biology↗

bioRxiv2018

Repulsive Guidance Molecule Acts in Axon Branching in Caenorhabditis elegans

Repulsive guidance molecules (RGMs) are evolutionarily conserved proteins implicated in repulsive axon guidance. Here we report the function of the Caenorhabditis elegans ortholog DRAG-1 in axon branching. The axons of hermaphrodite-specific neurons (HSNs) branch at the region abutting the vulval muscles and innervate these muscles to control egg laying. The drag-1 mutants exhibited defects in HSN axon branching in addition to a small body size and egg laying-defective phenotype. DRAG-1 expression in the hypodermal cells was required for the branching of these axons. The C-terminal glycosylphosphatidylinositol anchor of DRAG-1 was important for its function. Genetic analyses suggested that the membrane receptor UNC-40, but neither SMA-1/{beta}H-spectrin nor SMA-5/MAP kinase 7, acts in the same pathway with DRAG-1 in HSN branching. We propose that DRAG-1 expressed in the hypodermis signals via the UNC-40 receptor expressed in HSNs to elicit branching activity of HSN axons.

developmental biology↗

bioRxiv2018

Maintenance of Cell Fates by Regulation of the Histone Variant H3.3 in Caenorhabditis elegans

HighlightsTLK-1 maintains cell fates by repression of selector genes\n\nTLK-1 and downstream H3 chaperone CAF1 inhibit H3.3 deposition\n\nLoss of sin-3 suppresses the defect in cell-fate maintenance of tlk-1 mutants\n\nAcH4-binding protein BET-1 is necessary for sin-3 suppression\n\nSummaryCell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone H4-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans tousled-like kinase TLK-1 and the histone H3 chaperone CAF1 maintain cell fate by preventing the incorporation of histone variant H3.3 into nucleosomes, thereby repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. In tlk-1 mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1. sin-3 mutation also suppressed abnormal H3.3 incorporation. Thus, we propose that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes.

developmental biology↗