A5043012221- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Neurogenesis and neuroplasticity mechanisms
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Retinal Development and Disorders
- Axon Guidance and Neuronal Signaling
- Cancer-related gene regulation
- Congenital heart defects research
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Nerve injury and regeneration
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Spinal Cord Injury Research
- Birth, Development, and Health
- Hippo pathway signaling and YAP/TAZ
- Connexins and lens biology
- Pluripotent Stem Cells Research
- Proteoglycans and glycosaminoglycans research
- Hedgehog Signaling Pathway Studies
- Fibroblast Growth Factor Research
- Genomics and Chromatin Dynamics
- Kruppel-like factors research
- Neonatal Respiratory Health Research
- Animal Genetics and Reproduction
University of Utah
2012-2024
Allen Institute for Brain Science
2007
University of Washington
1997-2002
Howard Hughes Medical Institute
2000-2002
University of California, San Diego
1993-1997
We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required differentiation. isolated promoter region nacre contains Tcf/Lef binding sites, which can mediate responsiveness. This binds Lef1 protein in vitro, reporter construct strongly repressed by dominant-negative Tcf melanoma cells. Mutation sites abolishes function vivo. signaling therefore directly activates turn leads
While Wnt/beta-catenin signaling is known to be involved in the development of neural crest cells zebrafish, it unclear which Wnts are involved, and when they required. To address these issues we employed a zebrafish line that was transgenic for an inducible inhibitor signaling, inhibited endogenous at discrete times development. Using this approach, defined critical period Wnt initial induction crest, distinct from later pigment specified crest. Blocking during early interfered with...
Zebrafish regenerate their fins via the formation of a population progenitor cells, blastema. Wnt/β-catenin signaling is essential for blastemal cell proliferation and patterning overlying epidermis. Yet, we find that β-catenin neither active in epidermis nor majority proliferative cells. Rather, tissue-specific pathway interference indicates Wnt nonproliferative distal blastema required proximal blastema, cells lining osteoblasts directs osteoblast differentiation. Thus, regulates epidermal...
The adult blood system is established by hematopoietic stem cells (HSCs), which arise during development from an endothelial-to-hematopoietic transition of comprising the floor dorsal aorta. Expression aortic runx1 has served as early marker HSC commitment in zebrafish embryo, but recent studies have suggested that specification begins convergence posterior lateral plate mesoderm (PLM), well before aorta formation and transcription. Further understanding earliest stages necessitates earlier...
Caudalizing factors operate in the context of Wnt/beta-catenin signaling to induce gene expression discrete compartments along rostral-caudal axis developing vertebrate nervous system. In zebrafish, basal repression caudal genes is achieved through function Headless (Hdl), a Tcf3 homolog. this study, we show that second homolog, Tcf3b, limits caudalization caused by loss Hdl and although Lef/Tcf family member can rescue hdl mutants, Lef1 cannot. Wnts antagonize mediated derepression...
Although the functional importance of hypothalamus has been demonstrated throughout vertebrates, mechanisms controlling neurogenesis in this forebrain structure are poorly understood. We report that canonical Wnt signaling acts through Lef1 to regulate zebrafish hypothalamus. show is required for proneural and neuronal gene expression, differentiation posterior Furthermore, we find process dependent on Wnt8b, a ligand pathway expressed hypothalamus, both Wnt8b act mediate β-catenin-dependent...
Epithelia provide a critical protective barrier for our organs and are also the sites where most carcinomas form. Most studies on epithelia use cell culture or organisms high-resolution live imaging is inaccessible without invasive techniques. Here, we introduce developing zebrafish epidermis as an excellent in vivo model system studying living epithelium. We developed tools to fluorescently tag specific epithelial types express genes mosaic fashion using five GAL4 lines identified from...
Miles–Carpenter syndrome (MCS) was described in 1991 as an XLID with fingertip arches and contractures mapped to proximal Xq. Patients had microcephaly, short stature, mild spasticity, thoracic scoliosis, hyperextendable MCP joints, rocker-bottom feet, hyperextended elbows knees. A mutation, p.L66H, ZC4H2, identified a re-sequencing project. Additional screening of linked families next generation sequencing three ZC4H2 mutations: p.R18K, p.R213W p.V75in15aa. The shared some relevant clinical...
Wnt growth factors acting through the canonical intracellular signaling cascade play fundamental roles during vertebrate brain development. In particular, is crucial for normal development of dorsal midbrain, future optic tectum. Wnts act both as patterning signals and regulators cell growth. developing tectum, mitogenic; however, mechanism function not known. As a step towards better understanding this mechanism, we have identified two new targets, closely linked zic2a zic5 genes. Using...
Wnt signaling regulates multiple aspects of vertebrate central nervous system (CNS) development, including neurogenesis. However, genomes can contain up to 25 genes, the functions which are poorly characterized partly due redundancy in their expression. To identify candidate genes as mediators pathway activity specific brain progenitor zones, we have performed a comprehensive expression analysis at three different stages during zebrafish development. Antisense RNA probes for 21 were...
Abstract Background FOXP2 is a forkhead transcription factor critical for normal development of language in humans, but little known its broader function and regulation during central nervous system (CNS) development. We report here that lef1 , member the Lef/Tcf family factors activated by Wnt signaling, regulates foxP2 embryogenesis, we isolate novel enhancers which are -dependent. Results Loss, knock down, or inhibition led to loss expression. isolated DNA fragments from genomic region as...