A5019191395- Congenital heart defects research
- Lymphatic System and Diseases
- Developmental Biology and Gene Regulation
- FOXO transcription factor regulation
- Angiogenesis and VEGF in Cancer
- Hippo pathway signaling and YAP/TAZ
- Renal and related cancers
- Corneal surgery and disorders
- Corneal Surgery and Treatments
- Pluripotent Stem Cells Research
- Glaucoma and retinal disorders
- Cancer Cells and Metastasis
- Hedgehog Signaling Pathway Studies
- Kruppel-like factors research
- Congenital Heart Disease Studies
- Epigenetics and DNA Methylation
- Protein Tyrosine Phosphatases
- Genetic and Kidney Cyst Diseases
- Sympathectomy and Hyperhidrosis Treatments
- Zebrafish Biomedical Research Applications
- Biomarkers in Disease Mechanisms
- Wind Turbine Control Systems
- Reproductive Biology and Fertility
- Lymphatic Disorders and Treatments
- Connective Tissue Growth Factor Research
Northwestern University
2015-2024
Renal Research Institute
2016-2024
Kumamoto University
2019
Northwestern University
2017
Cardiovascular Institute Hospital
2014
Tokyo Women's Medical University
2013
The Graduate University for Advanced Studies, SOKENDAI
2013
National Institute of Genetics
2013
Hiroshima University
2013
Vanderbilt University Medical Center
1998-2010
ABSTRACT The murine genes, Foxc1 and Foxc2 (previously, Mf1 Mfh1), encode forkhead/winged helix transcription factors with virtually identical DNA-binding domains overlapping expression patterns in various embryonic tissues. Foxc1/Mf1 is disrupted the mutant, congenital hydrocephalus (Foxc1/Mf1ch), which has multiple developmental defects. We show here that, depending on genetic background, most homozygous mutants are born abnormalities of metanephric kidney, including duplex kidneys double...
The murine Foxc1/Mf1 and Foxc2/Mfh1 genes encode closely related forkhead/winged helix transcription factors with overlapping expression in the forming somites head mesoderm endothelial mesenchymal cells of developing heart blood vessels. Embryos lacking either Foxc1 or Foxc2, most compound heterozygotes, die pre- perinatally similar abnormal phenotypes, including defects axial skeleton cardiovascular system. However, major vessels do form. This suggested that have similar, dose-dependent...
Anterior segment developmental disorders, including Axenfeld–Rieger anomaly (ARA), variably associate with harmfully elevated intraocular pressure (IOP), which causes glaucoma. Clinically observed dysgenesis does not correlate IOP, however, and the etiology of glaucoma development is understood. The forkhead transcription factor genes Foxc1 (formerly Mf1) Foxc2 Mfh1) are expressed in mesenchyme from ocular drainage structures derive. Mutations human homolog Foxc1, FKHL7, cause dominant...
Haploinsufficiency of Tbx1 is likely a major determinant cardiac and craniofacial birth defects associated with DiGeorge syndrome. Although mice deficient in exhibit pharyngeal aortic arch defects, the developmental program mechanisms through which functions are relatively unknown. We identified single cis -element upstream that recognized winged helix/forkhead box (Fox)-containing transcription factors was essential for regulation endoderm head mesenchyme. The regulatory region responsive...
Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage major risk factor for the development glaucoma. Here, we demonstrated that genetic disruption angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features glaucoma, including retinal ganglion degeneration vision loss. Eyes from mice with induced deletion Angpt1 Angpt2 (A1A2Flox(WB)...
BackgroundRecent studies have shown that in the developing embryo, arterial and venous identity is established by genetic mechanisms before circulation begins. Vascular endothelial growth factor (VEGF) signaling its downstream Notch pathway play critical roles cell fate determination. We recently Foxc1 Foxc2, two closely related Fox transcription factors, are essential for specification during development directly inducing of Delta-like 4 (Dll4), a ligand receptors. However, basic whereby...
Significance Stem cells (SCs) of the hair follicle (HF) undergo cyclical bouts activity during which regeneration occurs. They reside in a specialized niche, bulge, confers upon them extended periods quiescence. Here, we identify Forkhead box C1 (FOXC1) as key transcriptional regulator HFSC and bulge maintenance. Loss FOXC1 reduces threshold for activation, causing excessive usage dramatically shortening between growth cycles. Additionally, signs weakened cellular junctions are seen within...
Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, determined that linked SNPs influence FOXC1 transcript levels demonstrated patients as young 1 year of age altered CSVD. MRI missense nonsense mutations well FOXC1-encompassing segmental...
Mice nullizygous for <i>Plcg</i>1 cease growing at early to mid-gestation. An examination of carefully preserved wild-type embryos shows clear evidence erythropoiesis, but erythropoiesis is not evident in the same stage. The analyses embryonic materials demonstrate that absence <i>Plcg</i>1, erythroid progenitors cannot be detected yolk sac or embryo body by three different assays, burst-forming units, colony-forming and analysis developmental marker Ter119. However, non-erythroid...
The Notch signaling pathway is a critical component of vascular formation and morphogenesis in both development disease. Compelling evidence indicates that required for the induction arterial-cell fate during selection endothelial tip stalk cells sprouting angiogenesis. In mammals, two four receptors (Notch1 Notch4) three five ligands (Jagged1, Dll1, Dll4) are predominantly expressed important many aspects biology. During arterial cell-fate angiogenesis, roles Notch1 Notch4 thought to be...
Angiopoietin-1 (Ang1) regulates both vascular quiescence and angiogenesis through the receptor tyrosine kinase Tie2. We another group previously showed that Ang1 Tie2 form distinct signaling complexes at cell-cell cell-matrix contacts. further demonstrated former up-regulates Notch ligand delta-like 4 (Dll4) only in presence of Because Dll4/Notch signal restricts sprouting promotes stabilization, we investigated mechanism how Ang1/Tie2 induces Dll4 expression to clarify role signal-mediated...
Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which Forkhead box transcription factor FoxC1 regulates development. Murine Foxc1 is essential development ocular anterior segment, and in humans, mutations have been identified Axenfeld-Rieger syndrome, disorder characterized segment dysgenesis. We show that FOXC1 also lead angiogenesis, mice homozygous either global (Foxc1(-/-)) or neural crest...
The lymphatic vasculature is essential for maintaining interstitial fluid homeostasis, and dysfunctional lymphangiogenesis contributes to various pathological processes, including inflammatory disease tumor metastasis. Mutations in FOXC2 are dominantly associated with late-onset lymphedema; however, the precise role of a closely related factor, FOXC1, system remains largely unknown. Here we identified molecular cascade by which FOXC1 regulate ERK signaling vessel growth. In mice, endothelial...
Mutations in the transcription factor FOXC2 are predominately associated with lymphedema. Herein, we demonstrate a key role for related FOXC1, addition to FOXC2, regulating cytoskeletal activity lymphatic valves. FOXC1 is induced by laminar, but not oscillatory, shear and inducible, endothelial-specific deletion impaired postnatal valve maturation mice. However, of Foxc2 degeneration, which exacerbated Foxc1; mutants. knockdown (KD) human endothelial cells increased focal adhesions actin...