- Wnt/β-catenin signaling in development and cancer
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Animal Genetics and Reproduction
- Genomics and Chromatin Dynamics
- Tissue Engineering and Regenerative Medicine
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neonatal Respiratory Health Research
- Fibroblast Growth Factor Research
- Axon Guidance and Neuronal Signaling
- Proteoglycans and glycosaminoglycans research
- Connective tissue disorders research
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Turbomachinery Performance and Optimization
- Kruppel-like factors research
- Erythrocyte Function and Pathophysiology
- Zebrafish Biomedical Research Applications
- Genetics and Neurodevelopmental Disorders
- Combustion and flame dynamics
National Institutes of Natural Sciences
2016-2025
National Institute for Basic Biology
2016-2025
The Graduate University for Advanced Studies, SOKENDAI
2015-2024
The Exploratory Research Center on Life and Living Systems
2021-2023
Living Systems (United States)
2021-2022
Okazaki Institute for Integrative Bioscience
2008-2018
Tohoku University
1989-2012
Teikyo University
2011
Toshiba (Japan)
2011
Harvard University
1998-2009
Embryonic patterning in vertebrates is dependent upon the balance of inductive signals and their specific antagonists. We show that Noggin, which encodes a bone morphogenetic protein (BMP) antagonist expressed node, notochord, dorsal somite, required for normal mouse development. Although Noggin has been implicated neural induction, examination null mutants indicates not essential this process. However, subsequent growth tube. Early BMP-dependent cell fates, roof plate crest, form absence...
Amphibian studies have implicated Wnt signaling in the regulation of mesoderm formation, although direct evidence is lacking. We characterized expression 12 mammalian Wnt-genes, identifying three that are expressed during gastrulation. Only one these, Wnt-3a, extensively cells fated to give rise embryonic mesoderm, at egg cylinder stages. A likely null allele Wnt-3a was generated by gene targeting. All Wnt-3a-/Wnt-3a- embryos lack caudal somites, a disrupted notochord, and fail form tailbud....
Ror2 is an orphan receptor, belonging to the Ror family of receptor tyrosine kinases. Although has been shown play crucial roles in developmental morphogenesis, precise signalling events that mediates remain elusive. Since possesses extracellular cysteine-rich domain (CRD) resembles Wnt-binding sites Frizzled (Fz) proteins, it conceivable interacts with members Wnt family.Both Ror2-/- and Wnt5a-/- mice exhibit dwarfism, facial abnormalities, short limbs tails, dysplasia lungs genitals,...
Terry P. Yamaguchi, Shinji Takada, Yoshiaki Yoshikawa, Nongying Wu, and Andrew McMahon Department of Molecular Cellular Biology, Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138 USA; Center for Developmental Graduate School Science, Kyoto Kitashirakawa, Sakyo-ku, 606-8502, Japan; Kondoh Differentiation Signaling Project, Exploratory Research Advanced Technology (ERATO), Japan Science Corporation (JST), 606-8305, Dermatology, Medicine, 606-8501,
Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations FGF receptors (FGFR) cause craniosynostosis, premature fusion skull, and dwarfism syndromes. Disruption Fgfr3 results prolonged long bones vertebrae. However, role that FGFs actually play embryo remains unclear. Here we show Fgf18 expressed required for osteogenesis chondrogenesis mouse embryo. both osteogenic mesenchymal cells differentiating osteoblasts during...
A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol glucose metabolism. The production of mice lacking revealed deficiency led to increased plasma levels fed a high-fat diet, because the decreased hepatic clearance chylomicron remnants. In addition, when LRP5-deficient showed markedly impaired tolerance. islets had marked reduction intracellular...
Microphthalmia-associated transcription factor (Mitf) plays a critical role in the development of neural crest-derived melanocytes. Here, we show that exogenously added Wnt-3a protein, an intercellular signaling molecule, up-regulates expression endogenous melanocyte-specific Mitf (Mitf-M) mRNA cultured The promoter humanMITF gene (MITF-M promoter) contains functional LEF-1-binding site, which is bound vitro by LEF-1 and confers preferential on reporter melanocytes melanoma cells, as judged...
Mammalian tooth crowns have precise functional requirements but cannot be substantially remodeled after eruption. In developing teeth, epithelial signaling centers, the enamel knots, form at future cusp positions and are first signs of patterns that distinguish species. We report ectodin, a secreted bone morphogenetic protein (BMP) inhibitor, is expressed as "negative" image mouse knots. Furthermore, we show ectodin-deficient mice enlarged highly altered patterns, extra teeth. Unlike in...
In the developing spinal cord, signals from roof plate are required for development of three classes dorsal interneuron: D1, D2, and D3, listed to ventral. Here, we demonstrate that absence Wnt1 Wnt3a, normally expressed in plate, leads diminished D1 D2 neurons a compensatory increase D3 neuron populations. This occurs without significantly altered expression BMP related genes plate. Moreover, Wnt3a protein induces markers isolated medial region chick neural Noggin does not interfere with...
Mice homozygous for the recessive mutation vestigial tail (vt), which arose spontaneously on Chromosome 11, exhibit vertebral abnormalities, including loss of caudal vertebrae leading to shortening tail. Wnt-3a, a member wingless family secreted glycoproteins, maps same chromosome. Embryos null in Wnt-3a (Wnt-3a(neo)) have complete absence bud development and are truncated rostral hindlimbs. Several lines evidence reveal that vt is hypomorphic allele Wnt-3a. We show cosegregate...
Background: Wnt‐3a is an intercellular signalling molecule that involved in a variety of morphogenetic events. However, the molecular mechanisms underlying are poorly understood. We have sought to establish vitro systems assay activity this protein and investigate its biological roles. Results: prepared mouse L cells transfected with cDNA, found their β‐catenin level was up‐regulated. When conditioned medium (CM) collected from cultures transfectants added nontransfected cells, latter also...
The inner ear is partitioned along its dorsal/ventral axis into vestibular and auditory organs, respectively. Gene expression studies suggest that this subdivision occurs within the otic vesicle, tissue from which all structures are derived. While specification of ventral fates dependent on Shh secreted notochord, nature signal responsible for dorsal development has not been described. In study, we demonstrate Wnt signaling active in regions where it functions to regulate genes ( Dlx5/6 Gbx2...
The receptor tyrosine kinase Ror2 plays important roles in developmental morphogenesis. It has recently been shown that mediates Wnt5a-induced noncanonical Wnt signaling by activating the Wnt–JNK pathway and inhibiting β-catenin–TCF pathway. However, function of leading to cell migration is largely unknown. We show, using genetically different or manipulated cultured cells, critical for Wnt5a-induced, but not Wnt3a-induced, migration. Ror2-mediated requires extracellular cysteine-rich domain...
Backgrounds A mouse receptor tyrosine kinase (RTK), mRor2, which belongs to the Ror‐family of RTKs consisting at least two structurally related members, is primarily expressed in heart and nervous system during development. To elucidate function we generated mice with a mutated mRor2 locus. Results Mice homozygous mutation died just after birth, exhibiting dwarfism, severe cyanosis, short limbs tails. Whole‐mount situ hybridization analysis showed that was branchial arches, limb/tailbuds,...
ABSTRACT Signals originating from tissues surrounding somites are involved in mediolateral and dorsoventral patterning of the differentiation myotome. Wnt-1 Wnt-3a, which encode members Wnt family cystein-rich secreted signaling molecules, coexpressed at dorsal midline developing neural tube, an area adjacent to dorsomedial portion somite. Several lines evidence indicate that Wnt-3a have ability induce development medial somites, as well myogenesis. To address whether these signalings really...