A5066338070- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Tissue Engineering and Regenerative Medicine
- Muscle Physiology and Disorders
- Genetics and Neurodevelopmental Disorders
- Chromosomal and Genetic Variations
- Renal and related cancers
- CRISPR and Genetic Engineering
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Fish biology, ecology, and behavior
- Biocrusts and Microbial Ecology
- Genomic variations and chromosomal abnormalities
- Aquatic life and conservation
- Algal biology and biofuel production
- Nerve injury and regeneration
- Hippo pathway signaling and YAP/TAZ
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
Osaka University
2020-2023
Harvard Stem Cell Institute
2017-2023
Brigham and Women's Hospital
2017-2023
Niigata University
2022
Gunma University
2020-2022
Harvard University
2017-2020
National Institute of Genetics
2007-2018
Inserm
2015-2018
Centre National de la Recherche Scientifique
2015-2018
Institut de génétique et de biologie moléculaire et cellulaire
2015-2018
The metameric structures in vertebrates are based on the periodicity of somites that formed one by from anterior end presomitic mesoderm (PSM). timing and spacing somitogenesis regulated segmentation clock, which is characterized oscillation several signaling pathways mice. temporal information needs to be translated into a spatial pattern so-called determination front, at cells become responsive clock signal. transcription factor Mesp2 plays crucial role this process, regulating segmental...
The Mesp2 transcription factor plays essential roles in segmental border formation and the establishment of rostro-caudal patterning within a somite. A possible target gene, Ripply2, was identified by microarray as being downregulated Mesp2-null mouse. Ripply2 encodes putative transcriptional co-repressor containing WRPW motif. We find that binds to gene enhancer, indicating is direct Mesp2. then examined whether responsible for repression genes under control generating Ripply2-knockout...
ABSTRACT Body skeletal muscles derive from the paraxial mesoderm, which forms in posterior region of embryo. Using microarrays, we characterize novel mouse presomitic mesoderm (PSM) markers and show that, unlike abrupt transcriptome reorganization PSM, neural tube differentiation is accompanied by progressive changes. The early stages can be efficiently recapitulated vitro using human pluripotent stem cells. While Wnt activation alone induce PSM markers, acquisition a committed fate...
Notch signaling exerts multiple roles during different steps of mouse somitogenesis. We have previously shown that segmental boundaries are formed at the interface activity boundary, suggesting importance on/off state for boundary formation. However, a recent study has embryos expressing Notch-intracellular domain (NICD) throughout presomitic mesoderm (PSM) can still form more than ten somites, indicating NICD is dispensable To clarify this discrepancy in our current study, we created...
Abstract In the past decades, function of Wnt canonical pathway during embryogenesis has been intensively investigated; however, little survey neonatal and adult tissues made, role this remains largely unknown. To investigate its in mature tissues, we generated two new reporter transgenic mouse lines, ins‐TOPEGFP ins‐TOPGAL, that drive EGFP β‐galactosidase expression under TCF/β‐catenin, respectively. obtain accurate pattern, flanked these transgenes with HS4 insulator to reduce chromosomal...
The T-box transcription factor Tbx6 controls the expression of Mesp2, which encodes a basic helix-loop-helix that has crucial roles in somitogenesis. In cultured cells, binding to Mesp2 enhancer region is essential for activation by Notch signaling. However, it not known whether this required vivo. Here we report an knockout mouse bearing mutations two sites does express presomitic mesoderm. This absence leads impaired skeletal segmentation identical reported Mesp2-null mice, indicating...
In germ cells, early embryos, and stem cells of animals, PIWI-interacting RNAs (piRNAs) have an important role in silencing retrotransposons, which are vicious genomic parasites, through transcriptional post-transcriptional mechanisms. To examine whether the piRNA pathway can be used to silence genes interest we generated knock-in mice a foreign DNA fragment was inserted into region generating pachytene piRNAs. The sequence transcribed, resulting RNA processed yield piRNAs postnatal testes....
Cyclin-dependent kinase 8 (CDK8) is a member of the CDK/Cyclin module mediator complex. A recent study reported that heterozygous missense CDK8 mutations cause neurodevelopmental disorder in humans. The mechanistic basis CDK8-related has yet to be delineated. Here, we report 2 patients with de novo within domain along results vitro and vivo functional analyses using zebrafish model. Patient 1 had intellectual disabilities congenital anomalies. Exome showed patient p.G28A variant...
The metameric structure in vertebrates is based on the periodic formation of somites from anterior end presomitic mesoderm (PSM). segmentation boundary defined by Tbx6 expression domain, whose limit determined protein destabilization via Ripply2. However, molecular mechanism this process poorly understood. Here, we show that Ripply2 directly binds to cultured cells without changing stability Tbx6, indicating an unknown for degradation vivo. We succeeded reproducing vivo events using a mouse...
In vertebrate embryos, the canonical Wnt ligand primes formation of dorsal organizers that govern dorsal-ventral patterns by secreting BMP antagonists. contrast, in Drosophila Toll-like receptor (Tlr)-mediated NFκB activation initiates patterning, wherein Wnt-mediated negative feedback regulation Tlr/NFκB generates a antagonist-secreting signalling centre to control pattern. Although both and antagonist are conserved among species, involvement organizer remains unclear. By imaging genetic...
Abstract Formation of the body vertebrate embryos proceeds sequentially by posterior addition tissues. While this process depends on aerobic glycolysis acting upstream Wnt signaling in tail bud cells, molecular details regulation are unknown. Here we used chicken and human bud-like cells differentiated vitro from iPS to show that acts increasing intracellular pH (pHi) cells. This promotes β-catenin acetylation leading activation choice a mesodermal fate at expense neural precursors. Our data...
Summary The French and Japanese Developmental Biology Societies, teaming up with Human Frontier Science Program, were eager to meet back in person November 2022 the lovely city of Strasbourg. Top scientists developmental biology field from France Japan, but also United States, Kingdom, Switzerland or Germany shared their exciting science during 4 days this meeting. Core fields such as morphogenesis, patterning, cell identity, state transition, notably at single level, well represented, a...
Mammalian embryos transiently exhibit aerobic glycolysis (Warburg effect), a metabolic adaptation also observed in cancer cells. The role of this particular type metabolism during vertebrate organogenesis is currently unknown. Here, we provide evidence for spatio-temporal regulation the posterior region mouse and chicken embryos. We show that glycolytic gradient established response to graded transcription enzymes downstream FGF signaling. demonstrate controls elongation embryonic axis by...
Abstract In vertebrates, body skeletal muscles and axial skeleton derive from the paraxial mesoderm which flanks neural tube notochord. The forms in posterior region of embryo as presomitic (PSM), generates embryonic segments called somites. Here, we characterized gene signatures identified using microarray series mouse PSM compared transcriptome dynamics to that developing tube. contrast where an abrupt reorganisation occurs at level determination front, show changes are progressive during...