Nishiwaki K (1999) Genetics "Mutations affecting symmetrical migration of distal tip cells in Caenorhabditis elegans."

Nishiwaki K

[Genetics, 1999]

The rotational symmetry of the Caenorhabditis elegans gonad arms is generated by the symmetrical migration of two distal tip cells (DTCs), located on the anterior and posterior ends of the gonad primordium. Mutations that cause asymmetrical migration of the two DTCs were isolated. All seven mutations were recessive and assigned to six different complementation groups. vab-3(k121) and vab-3(k143) affected anterior DTC migration more frequently than posterior, although null mutants showed no bias. The other five mutations, mig-14(k124), mig-17(k113), mig-18(k140), mig-19(k142), and mig-20(k148), affected posterior DTC migration more frequently than anterior. These observations imply that the migration of each DTC is regulated differently. mig-14 and mig-19 also affected the migration of other cells in the posterior body region. Four distinct types of DTC migration abnormalities were defined on the basis of the mutant phenotypes. vab-3; mig-14 double mutants exhibited the types of DTC migration defects seen for vab-3 single mutants. Combination of mig-17 and mig-18 or mig-19, which are characterized by the same types of posterior DTC migration defects, exhibited strong enhancement of anterior DTC migration defects, suggesting that they affect the same or parallel pathways regulating anterior DTC migration.

Nishiwaki K et al. (2000) Science "A metalloprotease disintegrin that controls cell migration in Caenorhabditis elegans."

Matsumoto K, Hisamoto N, Nishiwaki K

[Science, 2000]

In Caenorhabditis elegans, the gonad acquires two U-shaped arms by the directed migration of its distal tip cells (DTCs) along the body wall basement membranes. Correct migration of DTCs requires the mig-17 gene, which encodes a member of the metalloprotease-disintegrin protein family. The MIG-17 protein is secreted from muscle cells of the body wall and localizes in the basement membranes of gonad. This localization is dependent on the disintegrin-like domain of MIG-17 and its catalytic activity. These results suggest that the MIG-17 metalloprotease directs migration of DTCs by remodeling the basement membrane.

Nishiwaki K et al. (1998) Mol Gen Genet "Mutations in genes encoding extracellular matrix proteins suppress the emb-5 gastrulation defect in Caenorhabditis elegans."

Nishiwaki K, Miwa J

[Mol Gen Genet, 1998]

The second division of the gut precursor E cells is lethally accelerated during Caenorhabditis elegans gastrulation by mutations in the emb-5 gene, which encodes a presumed nuclear protein. We have isolated suppressor mutations of the temperature-sensitive allele emb-5(hc61), screened for them among dpy and other mutations routinely used as genetic markers, and identified eight emb-5 suppressor genes. Of these eight suppressor genes, at least four encode extracellular matrix proteins, i.e., three collagens and one proteoglycan. The suppression of the emb-5 gastrulation defect seemed to require the maternal expression of the suppressors. Phenotypically, the suppressors by themselves slowed down early embryonic cell divisions and corrected the abnormal cell-division sequence of emb-5 mutant embryos. We propose an indirect stress-response mechanism to be the main cause of the suppression because: (1) none of these suppressors is specific, either to particular temperature-sensitive emb-5 alleles or to the emb-5 gene; (2) suppressible alleles of genes, reported here or elsewhere, are temperature sensitive or weak; (3) the suppression is not strong but marginal; (4) the suppression itself shows some degree of temperature dependency; and (5) none of the extracellular matrix proteins identified here is known to be expressed in oocytes or early embryos, despite the present observation that the suppression is maternal.

Nishiwaki K et al. (2004) Nat Cell Biol "An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans."

Kubota Y, Chigira Y, Hisamoto N, Schvarzstein M, Matsumoto K, Roy SK, Nishiwaki K, Jigami Y, Suzuki M

[Nat Cell Biol, 2004]

In the nematode Caenorhabditis elegans, the gonad acquires two U-shaped arms through the directed migration of its distal tip cells (DTCs), which are located at the tip of the growing gonad arms(1). A member of the ADAM (a disintegrin and metalloprotease) family, MIG-17, regulates directional migration of DTCs: MIG-17 is synthesized and secreted from the muscle cells of the body wall, and diffuses to the gonad where it is required for DTC migration(2). The mig-23 mutation causes defective migration of DTCs and interacts genetically with mig-17. Here, we report that mig-23 encodes a membrane-bound nucleoside diphosphatase (NDPase) required for glycosylation and proper localization of MIG-17. Our findings indicate that an NDPase affects organ morphogenesis through glycosylation of the MIG-17 ADAM protease.

Nishiwaki K et al. (1993) Mol Gen Genet "emb-5, a gene required for the correct timing of gut precursor cell division during gastrulation in Caenorhabditis elegans, encodes a protein similar to the yeast nuclear protein SPT6."

Miwa J, Sano T, Nishiwaki K

[Mol Gen Genet, 1993]

The emb-5 gene is required for the correct timing of division of gut precursor cells during gastrulation in Caenorhabditis elegans. We have now characterized the molecular structure of emb-5. The predicted emb-5-encoded protein (EMB-5) possesses an extremely acidic amino-terminus and overall similarity to the Saccharomyces cerevisiae nuclear protein SPT6, which has been shown to affect the transcription of a variety of genes and suggested to play a role in chromatin assembly or modification. EMB-5 may function in the control of cell cycle timing by modulating chromatin structure and consequently affects morphogenesis of C. elegans.

Ihara S et al. (2008) FEBS J "Stage-specific activation of MIG-17/ADAMTS controls cell migration in Caenorhabditis elegans."

Ihara S, Nishiwaki K

[FEBS J, 2008]

The activation of ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family proteases depends on removal of the prodomain. Although several studies suggest that ADAMTS activities play roles in development, homeostasis and disease, it remains unclear when and where the enzymes are activated in vivo. MIG-17, a Caenorhabditis elegans glycoprotein belonging to the ADAMTS family, is secreted from the body wall muscle cells and localizes to the gonadal basement membrane to control the migration of gonadal distal tip cells. Here, we developed a monoclonal antibody that recognizes the N-terminal neo-epitope of the activated MIG-17. In western blotting, the antibody specifically detected the activated form, the signal for which dramatically increased during the third and fourth larval stages, when MIG-17 is required to direct distal tip cell migration. In in situ staining, the monoclonal antibody recognized the activated form in the basement membrane, whereas it failed to detect a processing-resistant mutant form localized to the basement membrane. MIG-17 was activated in the basement membranes of the muscle, intestine and gonad in the third larval stage, and downregulated in nongonadal basement membranes in young adults and in gonadal basement membranes in older adults. Thus, the activation of MIG-17 is regulated in a spatiotemporal manner during C. elegans development. This is the first report demonstrating the regulated activation of an ADAMTS protein in vivo. Our results suggest that monoclonal antibodies against neo-epitopes have potential as powerful tools for detecting activation of ADAMTSs during development and in disease pathogenesis.

Shibata Y et al. (2014) Worm "Maintenance of cell fates through acetylated histone and the histone variant H2A.z in C. elegans."

Nishiwaki K, Shibata Y

[Worm, 2014]

Maintenance of cell fates is essential for the development and homeostasis of multicellular organisms and involves the preservation of the expression status of selector genes that control many target genes. Epigenetic marks have pivotal roles in the maintenance of gene expression status, as occurs with methylation on lysine 27 of histone H3 (H3K27me) for Hox gene regulation. In contrast, because the levels of histone acetylation decrease during the mitotic phase, acetylated histone has not been believed to contribute to the maintenance of cell fates. Because members of the bromodomain and extra terminal (BET) family bind to acetylated histones localized on mitotic chromosomes, it is possible that they may regulate the transcriptional status of genes throughout the cell cycle. In this commentary, we discuss the recent analyses of C. elegans BET family protein BET-1, which contributes to the maintenance of cell fates through the histone H2A variant HTZ-1/H2A.z. This mechanism represses transcription of selector genes in the genomic region where lysine 27 of histone H3 (H3K27) is demethylated by histone demethylase UTX-1. We discuss the possibility that BET-1 and HTZ-1 maintain the poised state of RNA polymerase II in the cell such that it is ready to respond to differentiation signals.

Tamai KK et al. (2007) Dev Biol "bHLH transcription factors regulate organ morphogenesis via activation of an ADAMTS protease in C. elegans."

Nishiwaki K, Tamai KK

[Dev Biol, 2007]

The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases plays important roles in animal development and pathogenesis. However, transcriptional regulation of ADAMTS proteins during development remains largely unexplored. Here we show that basic helix-loop-helix (bHLH) transcription factors regulate the expression of an ADAMTS protease that is required for gonad development in Caenorhabditis elegans. Mutations in the gene mig-24 cause shortened and swollen gonad arms due to a defect in gonadal leader cell migration, although leader cell specification appears to occur normally. The MIG-24 protein is a bHLH transcription factor of the Achaete-Scute family and is specifically expressed in gonadal leader cells. MIG-24 can physically interact with HLH-2, an E/Daughterless family bHLH transcription factor and bind the promoter region of gon-1, which encodes an ADAMTS protease required for gonadal leader cell migration. Mutations or RNA interference of mig-24 and hlh-2 severely impaired gon-1 expression and forced expression of GON-1 in leader cells in mig-24 mutants partially rescued the gonadal elongation defect. We propose that, unlike most previously characterized Achaete-Scute transcription factors that are involved in cell fate specification, MIG-24 acts with HLH-2 in specified cells to control cell migration by activating the expression of the GON-1 ADAMTS protease.

Kim HS et al. (2012) Worm "Nuclear positioning in the gonadal distal tip cells of C. elegans."

Nishiwaki K, Kim HS

[Worm, 2012]

Morphogenesis of the hermaphrodite gonad of Caenorhabditis elegans is directed by the U-shaped migration of the gonadal leader cells, which are called distal tip cells (DTCs). The nuclei of migrating DTCs are always positioned at the leading edge of the cells, even as these cells turn dorsally to contact the hypodermis and intestine. When the DTCs turn dorsally, VAB-10B1/spectraplakin acts in nuclear translocation by regulating the polarized growth of microtubules. The function of spectraplakin in nuclear positioning may be evolutionarily conserved. Here we discuss the possible reason for leading-edge positioning of the DTC nucleus.

Miwa J et al. (1989) Tanpakushitsu Kakusan Koso "[Developmental genetics of Caenorhabditis elegans]"

Nishiwaki K, Miwa J

[Tanpakushitsu Kakusan Koso, 1989]