A5023829156- Cleft Lip and Palate Research
- Craniofacial Disorders and Treatments
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- melanin and skin pigmentation
- dental development and anomalies
- Melanoma and MAPK Pathways
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
- RNA regulation and disease
- Cancer-related gene regulation
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Biochemical Analysis and Sensing Techniques
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ion Channels and Receptors
- Genomic variations and chromosomal abnormalities
- Congenital Ear and Nasal Anomalies
- Neuroscience and Neuropharmacology Research
- Renal and related cancers
- interferon and immune responses
- RNA Research and Splicing
University of Washington
1994-2025
University of Iowa
2013-2022
Institute of Cell Biology and Neurobiology
2011-2022
John Wiley & Sons (United States)
2017
Carver Bible College
2014
Cornell University
2008
University of Oregon
2000-2002
Oregon State University
1972
UtopiaCompression (United States)
1970
Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases Van der Woude syndrome (VWS), the most common syndromic form cleft lip and palate. In 8 45 VWS-affected families lacking a mutation IRF6, we found coding mutations grainyhead-like 3 (GRHL3). According to zebrafish-based assay, disease-associated GRHL3 abrogated periderm development were consistent with dominant-negative effect, contrast haploinsufficiency seen VWS caused by IRF6 mutations. mouse, all embryos Grhl3...
Abstract Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing genes that are characteristic of various types including endothelial, neural, and stem cells. Moreover, we have shown cells can participate in neovascularization vivo vasculogenic mimicry vitro, demonstrating these respond to microenvironmental cues manifest developmental plasticity. To explore this plasticity further, transplanted human metastatic into zebrafish blastula‐stage embryos monitored...
ABSTRACT The early patterning of mesoderm in the Xenopus embryo requires signals from several intercellular factors, including mesoderm-inducing agents that belong to fibroblast growth factor (FGF) and TGF-β families. In animal hemisphere explants (animal caps), basic FGF family member activin are capable converting pre-ectodermal cells a mesodermal fate, although is much more effective at inducing dorsal anterior than FGF. Using dominant-negative form type 1 receptor, we show an signal...
In zebrafish, cells at the lateral edge of neural plate become Rohon-Beard primary sensory neurons or crest. Delta/Notch signaling is required for crest formation. ngn1 expressed in neurons; inhibiting Ngn1 activity prevents cell formation but not other neurons. Reducing embryos lacking restores formation, indicating inhibits neurogenesis without actively promoting also later development dorsal root ganglion however, and are necessarily derived from same precursor cell. We propose that...
Microphthalmia-associated transcription factor (MITF) is the master regulator of melanocyte lineage. To understand how MITF regulates transcription, we used tandem affinity purification and mass spectrometry to define a comprehensive interactome identifying novel cofactors involved in DNA replication repair, chromatin organisation. We show that interacts with PBAF remodelling complex comprising BRG1 CHD7. essential for melanoma cell proliferation vitro normal development vivo. SOX10 actively...
Preplacodal ectoderm arises near the end of gastrulation as a narrow band cells surrounding anterior neural plate. This domain later resolves into discrete cranial placodes that, together with crest, produce paired sensory structures head. Unlike better-characterized little is known about early regulation preplacodal development. Classical models ectodermal patterning posit that identity specified by readout level Bmp signaling along DV gradient. More recent studies indicate Bmp-antagonists...
Molecular signatures specific to particular tumor types are required design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used drug development share such signatures. We developed similarity core analysis (SCA), a universal unsupervised computational framework extracting molecular features common lines. applied SCA mRNA/miRNA expression data from various sources, comparing melanoma metastases. The signature obtained was associated...
The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression genes associated with extracellular matrix (ECM) focal adhesion pathways human cells well regulators...
Mutations in the gene encoding transcription factor TFAP2A result pigmentation anomalies model organisms and premature hair graying humans. However, pleiotropic functions of its redundantly-acting paralogs have made precise contribution TFAP2-type activity to melanocyte differentiation unclear. Defining this may help explain why expression is reduced advanced-stage melanoma compared benign nevi. To identify genes with TFAP2A-dependent melanocytes, we profile zebrafish tissue mouse...
Development of the palate in vertebrates involves cranial neural crest migration, convergence facial prominences and extension cartilaginous framework. Dysregulation palatogenesis results orofacial clefts, which represent most common structural birth defects. Detailed analysis zebrafish revealed distinct mechanisms palatal morphogenesis: extension, proliferation integration. We show that wnt9a is required for wherein chondrocytes form a proliferative front, undergo morphological change...
Sensory hair cells are essential for hearing and balance. Their development from epithelial precursors has been extensively characterized with respect to transcriptional regulation, but not in terms of posttranscriptional influences. Here we report on the identification functional characterization an alternative-splicing regulator whose inactivation is responsible defective hair-cell development, deafness, impaired balance spontaneous mutant Bronx waltzer (bv) mouse. We used positional...
Abstract Renal agenesis is a devastating birth defect, and although genes encoding retinoic acid signaling components have been shown to be important for renal... (RA) one of the more extreme examples congenital anomalies kidney urinary tract (CAKUT). Bilateral renal almost invariably fatal at birth, unilateral can lead future health issues including end-stage disease. Genetic investigations identified several gene variants that cause RA, EYA1, LHX1, WT1. However, whereas compound null...
Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) lip with or without (CL/P) ~17 million markers in sub-Saharan Africans. After replication combined analyses, we identified novel loci CPO at near significance on chromosomes 2 (near CTNNA2) 19 SULT2A1). In situ hybridization of Sult2a1 mice showed expression SULT2A1 mesenchymal cells palate,...
In Finland, the frequency of isolated cleft palate (CP) is higher than that lip with or without (CL/P). This trend contrasts to in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study Finnish population and identified rs570516915, single nucleotide polymorphism highly enriched Finns, as strongly associated CP (P = 5.25 × 10−34, OR 8.65, 95% CI 6.11–12.25), not CL/P 7.2 10−5), significance. The risk allele rs570516915 parallels...
ABSTRACT Normal pattern formation during embryonic development requires the regulation of cellular competence to respond inductive signals. In Xenopus blastula, vegetal cells release mesoderm-inducing factors but themselves become endoderm, suggesting that may be prevented from expressing mesodermal genes in response signals they secrete. We show here addition low levels basic fibroblast growth factor (bFGF) induces ectopic expression markers Xbra, MyoD and muscle actin explants, even though...