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News Article | December 23, 2015
Site: phys.org

Some reptiles such as crocodilians and some turtles are known to display temperature-dependent sex determination (TSD), where the ambient temperature of the developing eggs determines the individual's sex. For example in the American alligator's eggs, incubation at 33 ºC produces mostly males, while incubation at 30 ºC produces mostly females. An international joint research team between Japan and the US have determined that the thermosensor protein TRPV4 is associated with TSD in the American alligator. The research has been published in Scientific Reports. The research team headed by Professor Taisen Iguchi of the National Institute for Basic Biology (Okazaki Institute for Integrative Bioscience) and PhD student Ryohei Yatsu of SOKENDAI (The Graduate University for Advanced Studies), in collaboration with Professor Makoto Tominaga of the National Institute for Physiological Sciences (Okazaki Institute for Integrative Bioscience) and Professor Louis J. Guillette Jr. and assistant professor Satomi Kohno of the Medical University of South Carolina, have investigated the molecular mechanism of how temperature determines sex. In their research using American alligators, they found that a thermosensitive protein called TRPV4 is present within the developing alligator gonad inside the egg. Alligator TRPV4 is responsive to warm temperatures near mid-30s, and can activate cell signaling by inducing calcium ion influx. The current study also demonstrates that by specific pharmacological inhibition of TPRV4 protein function in the developing egg, genes important for male development (for example, genes encoding anti-Müllerian hormone and SOX9) are influenced, and partial feminization at male producing temperatures have been observed. From these results the authors demonstrate that TRPV4 may significantly influence the male gonadal sex determination pathway at a molecular level during TSD in the alligator. This is the first demonstrated report of a biomolecule associated with regulation of the very unique temperature-dependent sex determination mechanism. PhD student Ryohei Yatsu said, "Reptiles can be difficult to study at times, but we were delighted to obtain such an interesting result and elucidate part of the alligator TSD mechanism. We still have much to research, but we are interested in how our results relate with other TSD species diversity and evolution". Professor Taisen Iguchi said, "Organisms that have adopted TSD systems may be more susceptible to the risks of environmental change, such as global warming. In future, we would like to know how an unstable environmental factor such as incubation temperature was able to establish itself as a sex determination factor." More information: Ryohei Yatsu et al. TRPV4 associates environmental temperature and sex determination in the American alligator, Scientific Reports (2015). DOI: 10.1038/srep18581


Sada A.,Sokendai | Hasegawa K.,National Institute of Genetics | Pin P.H.,Sokendai | Saga Y.,Sokendai | Saga Y.,National Institute of Genetics
Stem Cells | Year: 2012

Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. © AlphaMed Press.


Nishimura K.,National Institute of Genetics | Ishiai M.,Kyoto University | Horikawa K.,National Institute of Genetics | Fukagawa T.,SOKENDAI | And 4 more authors.
Molecular Cell | Year: 2012

DNA interstrand crosslinks (ICLs) are highly toxic lesions that stall the replication fork to initiate the repair process during the S phase of vertebrates. Proteins involved in Fanconi anemia (FA), nucleotide excision repair (NER), and translesion synthesis (TS) collaboratively lead to homologous recombination (HR) repair. However, it is not understood how ICL-induced HR repair is carried out and completed. Here, we showed that the replicative helicase-related Mcm family of proteins, Mcm8 and Mcm9, forms a complex required for HR repair induced by ICLs. Chicken DT40 cells lacking MCM8 or MCM9 are viable but highly sensitive to ICL-inducing agents, and exhibit more chromosome aberrations in the presence of mitomycin C compared with wild-type cells. During ICL repair, Mcm8 and Mcm9 form nuclear foci that partly colocalize with Rad51. Mcm8-9 works downstream of the FA and BRCA2/Rad51 pathways, and is required for HR that promotes sister chromatid exchanges, probably as a hexameric ATPase/helicase. © 2012 Elsevier Inc..


Hernandes M.,Sokendai
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Unawareness is analyzed under a framework due to Michael Franke. When a player is facing a game which she is unaware I propose a solution to choose an action to be performed. I discuss a game update raising a need for awareness dynamics, finally a Haskell implementation is proposed helping to sharpen our intuition about this topic. abstract environment. © 2012 Springer-Verlag.


Oginuma M.,SOKENDAI | Oginuma M.,National Institute of Genetics | Takahashi Y.,Japan National Institute of Health Sciences | Kitajima S.,Japan National Institute of Health Sciences | And 6 more authors.
Development | Year: 2010

Notch signaling exerts multiple roles during different steps of mouse somitogenesis. We have previously shown that segmental boundaries are formed at the interface of the Notch activity boundary, suggesting the importance of the Notch on/off state for boundary formation. However, a recent study has shown that mouse embryos expressing Notch-intracellular domain (NICD) throughout the presomitic mesoderm (PSM) can still form more than ten somites, indicating that the NICD on/off state is dispensable for boundary formation. To clarify this discrepancy in our current study, we created a transgenic mouse lacking NICD boundaries in the anterior PSM but retaining Notch signal oscillation in the posterior PSM by manipulating the expression pattern of a Notch modulator, lunatic fringe. In this mouse, clearly segmented somites are continuously generated, indicating that the NICD on/off state is unnecessary for somite boundary formation. Surprisingly, this mouse also showed a normal rostral-caudal compartment within a somite, conferred by a normal Mesp2 expression pattern with a rostral-caudal gradient. To explore the establishment of normal Mesp2 expression, we performed computer simulations, which revealed that oscillating Notch signaling induces not only the periodic activation of Mesp2 but also a rostral-caudal gradient of Mesp2 in the absence of striped Notch activity in the anterior PSM. In conclusion, we propose a novel function of Notch signaling, in which a progressive oscillating wave of Notch activity is translated into the rostral-caudal polarity of a somite by regulating Mesp2 expression in the anterior PSM. This indicates that the initial somite pattern can be defined as a direct output of the segmentation clock.


Okubo Y.,SOKENDAI | Okubo Y.,Japan National Institute of Health Sciences | Sugawara T.,National Institute of Genetics | Abe-Koduka N.,National Institute of Genetics | And 4 more authors.
Nature Communications | Year: 2012

The synchronized oscillation of segmentation clock is required to generate a sharp somite boundary during somitogenesis. However, the molecular mechanism underlying this synchronization in the mouse embryos is not clarified yet. We used both experimental and theoretical approaches to address this key question. Here we show, using chimeric embryos composed of wild-type cells and Delta like 1 (Dll1)-null cells, that Dll1-mediated Notch signalling is responsible for the synchronization mechanism. By analysing Lunatic fringe (Lfng) chimeric embryos and Notch signal reporter assays using a co-culture system, we further find that Lfng represses Notch activity in neighbouring cells by modulating Dll1 function. Finally, numerical simulations confirm that the repressive effect of Lfng against Notch activities in neighbouring cells can sufficiently explain the synchronization in vivo. Collectively, we provide a new model in which Lfng has a crucial role in intercellular coupling of the segmentation clock through a trans-repression mechanism. © 2012 Macmillan Publishers Limited. All rights reserved.


Aoki K.,National Institute of Genetics | Hayashi H.,SOKENDAI | Hayashi H.,National Institute of Genetics | Furuya K.,National Institute of Genetics | And 7 more authors.
Genes to Cells | Year: 2011

During open mitosis in higher eukaryotic cells, the nuclear envelope completely breaks down and then mitotic chromosomes are exposed in the cytoplasm. By contrast, mitosis in lower eukaryotes, including fungi, proceeds with the nucleus enclosed in an intact nuclear envelope. The mechanism of mitosis has been studied extensively in yeast, a closed mitosis organism. Here, we describe a form of mitosis in which the nuclear envelope is torn by elongation of the nucleus in the fission yeast Schizosaccharomyces japonicus. The mitotic nucleus of Sz. japonicus adopted a fusiform shape in anaphase, and its following extension caused separation. Finally, a tear in the nuclear envelope occurred in late anaphase. At the same time, a polarized-biased localization of nuclear pores was seen in the fusiform-shaped nuclear envelope, suggesting a compromise in the mechanical integrity of the lipid membrane. It has been known that nuclear membrane remains intact in some metazoan mitosis. We found that a similar tear of the nuclear envelope was also observed in late mitosis of the Caenorhabditis elegans embryo. These findings provide insight into the diversity of mitosis and the biological significance of breakdown of the nuclear envelope. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.


Wu Q.,SOKENDAI | Kanata K.,Osaka University | Saba R.,National Institute of Genetics | Deng C.-X.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | And 3 more authors.
Development (Cambridge) | Year: 2013

Testicular development in the mouse is triggered in somatic cells by the function of Sry followed by the activation of fibroblast growth factor 9 (FGF9), which regulates testicular differentiation in both somatic and germ cells. However, the mechanism is unknown. We show here that the nodal/activin signaling pathway is activated in both male germ cells and somatic cells. Disruption of nodal/activin signaling drives male germ cells into meiosis and causes ectopic initiation of female-specific genes in somatic cells. Furthermore, we prove that nodal/activin-A works directly on male germ cells to induce the male-specific gene Nanos2 independently of FGF9. We conclude that nodal/activin signaling is required for testicular development and propose a model in which nodal/activin- A acts downstream of fibroblast growth factor signaling to promote male germ cell fate and protect somatic cells from initiating female differentiation. © 2013. Published by The Company of Biologists Ltd.


Zhao W.,University of Tokyo | Ajima R.,SOKENDAI | Ajima R.,National Institute of Genetics | Ninomiya Y.,National Institute of Genetics | And 2 more authors.
Developmental Biology | Year: 2015

The precise border of somites formed during mouse somitogenesis is defined by a Tbx6 expression domain, which is established by Mesp2-mediated Tbx6 suppression in the anterior part of the presomitic mesoderm (PSM). Ripply2, a target of Mesp2, is proposed to be involved in this down-regulation because Ripply2 deficiency causes an anterior expansion of the Tbx6 domain, resembling the Mesp2-null phenotype. However, it is unclear whether Ripply2 acts on Tbx6 independently or in association with Mesp2. To address this question, we generated three sets of transgenic mice with the following Ripply2 expression patterns: (1) overexpression in the endogenous expression domain, (2) expression instead of Mesp2 (Ripply2-knockin), and (3) ectopic expression in the entire PSM. We found accelerated Tbx6 degradation in the embryos showing Ripply2 overexpression. In the Ripply2-knockin embryos, the anterior limit of Tbx6 domain was generated by Ripply2 even in the absence of Mesp2. Ectopic Ripply2 expression along the entire PSM suppressed Tbx6 and induced Sox2-positive neural tube formation at the bilateral domain, resembling the Tbx6-null phenotype. This phenotype resulted from Tbx6 protein and not mRNA elimination, suggesting the post-translational down-regulation of Tbx6 by Ripply2. Taken together, our results demonstrate that Ripply2 represses Tbx6 in a Mesp2-independent manner, which contributes to the accurate segmental border formation. © 2015 Elsevier Inc.


News Article | October 6, 2016
Site: phys.org

An international team of astronomers using the Subaru Telescope and led by a graduate student member of SOKENDAI (The Graduate University of Advanced Studies, Japan) has discovered companions circling "intermediate-mass" stars. These are stars that are heavier than the Sun and the companions were thought to be either planets or possibly small stars. The excellent performance of the Subaru Telescope enabled the detection of faint objects circling around three of six bright stars surveyed.

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