Details of a Researcher

Papers - Hirota, Yuki

Division display 21 - 32 of about 32 ／ All the affair displays >>

Various facets of vertebrate cilia: motility, signaling, and role in adult neurogenesis

Huang, Shihhui, Hirota, Yuki, Sawamoto, Kazunobu

PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES 85 ( 8 ) 324 - 336 2009.10

Research paper (scientific journal), ISSN 0386-2208

Access to Document (DOI)

Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility

Suzuki Toshimitsu, Miyamoto Hiroyuki, Nakahari Takashi, Inoue Ikuyo, Suemoto Takahiro, Jiang Bin, Hirota Yuki, Itohara Shigeyoshi, Saido Takaomi C., Tsumoto Tadaharu, Sawamoto Kazunobu, Hensch Takao K., Delgado-Escueta Antonio V., Yamakawa Kazuhiro

Human Molecular Genetics 18 ( 6 ) 1099 - 1109 2009

ISSN 0964-6906

Mutations in EFHC1 gene have been previously reported in patients with epilepsies, including those with juvenile myoclonic epilepsy. Myoclonin1, also known as mRib72-1, is encoded by the mouse Efhc1 gene. Myoclonin1 is dominantly expressed in embryonic choroid plexus, post-natal ependymal cilia, tracheal cilia and sperm flagella. In this study, we generated viable Efhc1-deficient mice. Most of the mice were normal in outward appearance, and both sexes were found to be fertile. However, the ventricles of the brains were significantly enlarged in the null mutants, but not in the heterozygotes. Although the ciliary structure was found intact, the ciliary beating frequency was significantly reduced in null mutants. In adult stages, both the heterozygous and null mutants developed frequent spontaneous myoclonus. Furthermore, the threshold of seizures induced by pentylenetetrazol was significantly reduced in both heterozygous and null mutants. These observations seem to further suggest that decrease or loss of function of myoclonin1 may be the molecular basis for epilepsies caused by EFHC1 mutations. © The Author 2009. Published by Oxford University Press. All rights reserved.

Access to Document (DOI)

Neurogenesis in the adult subventricular zone

Hirota Yuki, Sawamoto Kazunobu

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 53 ( 7 ) 863 - 869 2008.06

ISSN 0039-9450

Cyclin-dependent kinase 5 is required for control of neuroblast migration in the postnatal subventricular zone

Hirota Yuki, Ohshima Toshio, Kaneko Naoko, Ikeda Makiko, Iwasato Takuji, Kulkarni Ashok B., Mikoshiba Katsuhiko, Okano Hideyuki, Sawamoto Kazunobu

Journal of Neuroscience 27 ( 47 ) 12829 - 12838 2007.11

ISSN 0270-6474

At the lateral wall of the lateral ventricles in the adult rodent brain, neuroblasts form an extensive network of elongated cell aggregates called chains in the subventricular zone and migrate toward the olfactory bulb. The molecular mechanisms regulating this migration of neuroblasts are essentially unknown. Here, we report a novel role for cyclin-dependent kinase 5 (Cdk5), a neuronal protein kinase, in this process. Using in vitro and in vivo conditional knock-out experiments, we found that Cdk5 deletion impaired the chain formation, speed, directionality, and leading process extension of the neuroblasts in a cell-autonomous manner. These findings suggest that Cdk5 plays an important role in neuroblast migration in the postnatal subventricular zone. Copyright © 2007 Society for Neuroscience.

Access to Document (DOI)

Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum

Yamashita Toru, Ninomiya Mikiko, Acosta Pilar Hernández, García-Verdugo Jose Manuel, Sunabori Takehiko, Sakaguchi Masanori, Adachi Kazuhide, Kojima Takuro, Hirota Yuki, Kawase Takeshi, Araki Nobuo, Abe Koji, Okano Hideyuki, Sawamoto Kazunobu

Journal of Neuroscience 26 ( 24 ) 6627 - 6636 2006

ISSN 0270-6474

Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders. Copyright © 2006 Society for Neuroscience.

Access to Document (DOI)

The transmembrane protein, Tincar, is involved in the development of the compound eye in Drosophila melanogaster

Hirota Yuki, Sawamoto Kazunobu, Takahashi Kuniaki, Ueda Ryu, Okano Hideyuki

Development Genes and Evolution 215 ( 2 ) 90 - 96 2005.02

ISSN 0949-944X

We previously cloned and characterized the Drosophila gene, tincar (tinc), which encodes a novel protein with eight putative transmembrane domains. Here, we have studied the expression pattern and functions of tinc during developmental processes. Tinc mRNA is expressed in the central and peripheral nervous systems, and midgut during embryogenesis. In the third-instar larval eye disc, tinc mRNA is strongly expressed in all the differentiating ommatidial cells within and in the vicinity of the morphogenetic furrow. Loss-of-function analysis using the RNA-interference method revealed severe defects of eye morphogenesis during the late developmental stages. Our results suggested that tinc may have an indispensable role in the normal differentiation of ommatidial cells. © Springer-Verlag 2005.

Access to Document (DOI)

tincar encodes a novel transmembrane protein expressed in the Tinman-expressing cardioblasts of Drosophila

Hirota Yuki, Sawamoto Kazunobu, Okano Hideyuki

Mechanisms of Development 119 ( SUPPL. 1 ) 2002.12

ISSN 0925-4773

We cloned and characterized the Drosophila gene, tincar (tinc), which encodes a novel protein with eight putative transmembrane domains. The tinc mRNA was expressed specifically in four of the six pairs of cardioblasts in each segment, in a pattern identical to that of tinman (tin), a homeobox gene required for the specification of the dorsal vessel. In the non-Tin-expressing pairs of cardioblasts, tinc transcription seemed to be repressed by Seven-up. © 2003 Elsevier Science Ireland Ltd. All rights reserved.

Access to Document (DOI)

DN-cadherin is required for spatial arrangement of nerve terminals and ultrastructural organization of synapses

Iwai, Y, Hirota, Y, Ozaki, K, Okano, H, Takeichi, M, Uemura, T

MOLECULAR AND CELLULAR NEUROSCIENCE 19 ( 3 ) 375 - 388 2002.03

Research paper (scientific journal), ISSN 1044-7431

Access to Document (DOI)

Musashi and Seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development

Hirota Yuki, Okabe Masataka, Imai Takao, Kurusu Mitsuhiko, Yamamoto Atsuyo, Miyao Sachiyo, Nakamura Makoto, Sawamoto Kazunobu, Okano Hideyuki

Mechanisms of Development 87 ( 1-2 ) 93 - 101 1999.09

ISSN 0925-4773

We have examined the roles played by the Drosophila neural RNA-binding protein Musashi (MSI) in eye development. MSI expression was observed in the nuclei of all photoreceptor cells (R1-R8). Although a msi loss-of-function mutation resulted in only weak abnormalities in photoreceptor differentiation, we found that the msi eye phenotype was significantly enhanced in a seven in absentia (sina) background. sina is known to be involved in the degradation of the Tramtrack (TTK) protein, leading to the specification of the R7 fate. We demonstrated that MSI also functions to regulate TTK expression. The sina msi mutants showed significantly high ectopic expression of TTK69 and failure in the determination of the R1, R6, and R7 fates. Other photoreceptor cells also failed to differentiate with abnormalities occurring late in the differentiation process. These results suggest that MSI and SINA function redundantly to downregulate TTK in developing photoreceptor cells. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Access to Document (DOI)

The Drosophila Ral GTPase regulates developmental cell shape changes through the Jun NH₂-terminal kinase pathway

Sawamoto Kazunobu, Winge Per, Koyama Shinya, Hirota Yuki, Yamada Chiharu, Miyao Sachiyo, Yoshikawa Shingo, Jin Ming Hao, Kikuchi Akira, Okano Hideyuki

Journal of Cell Biology 146 ( 2 ) 361 - 372 1999.07

ISSN 0021-9525

The Ral GTPase is activated by RalGDS, which is one of the effector proteins for Ras. Previous studies have suggested that Ral might function to regulate the cytoskeleton; however, its in vivo function is unknown. We have identified a Drosophila homologue of Ral that is widely expressed during embryogenesis and imaginal disc development. Two mutant Drosophila Ral (DRal) proteins, DRal(G20V) and DRal(S25N), were generated and analyzed for nucleotide binding and GTPase activity. The biochemical analyses demonstrated that DRal(G20V) and DRal(S25N) act as constitutively active and dominant negative mutants, respectively. Overexpression of the wild-type DRal did not cause any visible phenotype, whereas DRal(G20V) and DRal(S25N) mutants caused defects in the development of various tissues including the cuticular surface, which is covered by parallel arrays of polarized structures such as hairs and sensory bristles. The dominant negative DRal protein caused defects in the development of hairs and bristles. These phenotypes were genetically suppressed by loss of function mutations of hemipterous and basket, encoding Drosophila Jun NH₂-terminal kinase kinase (JNKK) and Jun NH₂-terminal kinase (JNK), respectively. Expression of the constitutively active DRal protein caused defects in the process of dorsal closure during embryogenesis and inhibited the phosphorylation of JNK in cultured S2 cells. These results indicate that DRal regulates developmental cell shape changes through the JNK pathway.

Access to Document (DOI)

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development

Sawamoto Kazunobu, Yamada Chiharu, Kishida Shosei, Hirota Yuki, Taguchi Akiko, Kikuchi Akira, Okano Hideyuki

Oncogene 18 ( 11 ) 1967 - 1974 1999.03

ISSN 0950-9232

The small GTP-binding protein Ral is activated by RalGDS, one of the effector molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and Rac. Although previous studies suggest a role for Ral in the regulation of CDC42 and Rac, which are involved in arranging the cytoskeleton, its in in vivo function is largely unknown. To examine the effect of overexpressing Ral on development, transgenic Drosophila were generated that overexpress wild-type or mutated Ral during eye development. While wild-type Ral caused no developmental defects, expression of a constitutively activated protein resulted in a rough eye phenotype. Activated Rat did not affect cell fate determination in the larval eye discs but caused severe disruption of the ommatidial organization later in pupal development. Phalloidin staining showed that activated Ral perturbed the cytoskeletal structure and cell shape changes during pupal development. This phenotype is similar to that caused by RhoA overexpression. In addition, the phenotype was synergistically enhanced by the coexpression of RhoA. These results suggest that Ral functions to control the cytoskeletal structure required for cell shape changes during Drosophila development.

Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway (vol 5, pg 262, 1998)

Sawamoto, K, Taguchi, A, Hirota, Y, Yamada, C, Jin, MH, Okano, H

CELL DEATH AND DIFFERENTIATION 5 ( 6 ) 548 - 548 1998.06

Research paper (scientific journal), ISSN 1350-9047

　 Previous page - Next page 　