A5013624954- Retinal Development and Disorders
- Hippo pathway signaling and YAP/TAZ
- Zebrafish Biomedical Research Applications
- Developmental Biology and Gene Regulation
- Cellular Mechanics and Interactions
- Lipid metabolism and biosynthesis
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Connexins and lens biology
- Spaceflight effects on biology
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Glaucoma and retinal disorders
- melanin and skin pigmentation
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Corneal Surgery and Treatments
- Neurobiology and Insect Physiology Research
- Plant Molecular Biology Research
- Retinopathy of Prematurity Studies
- Advanced Fluorescence Microscopy Techniques
- interferon and immune responses
Medical College of Wisconsin
2011-2024
University of California, Davis
2017-2020
The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors signaling pathways have been shown to be important for RPE maintenance differentiation, but an understanding initial fate specification determination this cell type is lacking. We show that Yap/Taz-Tead activity necessary sufficient progenitors adopt identity in zebrafish. A...
To gain insights into the cellular mechanisms of neurogenesis, we analyzed retinal neuroepithelia deficient for Llgl1, a protein implicated in apicobasal cell polarity, asymmetric division, shape and cycle exit. We found that vertebrate Llgl1 retained overt but had expanded apical domains. progenitors also increased Notch activity reduced rates neurogenesis. Blocking function by depleting Rbpj restored normal Experimental expansion domain, through inhibition Shroom3, Significantly, wild-type...
To investigate the role of Hippo pathway signaling during vertebrate development transgenic zebrafish lines were generated and validated to dynamically monitor manipulate Yap/Taz-Tead activity. Spatial temporal analysis activity suggested importance cardiac precursor migration other developmental processes. When transcriptional co-activators, Yap Taz restricted from interacting with DNA-binding Tead transcription factors through expression a dominant negative transgene, precursors failed...
Significance Vertebrate retinal ganglion cells (RGCs) transmit all visual signals from the eye to brain, are pathogenic target in glaucoma, and require Atoh7 competence factor develop multipotent progenitors. transcription is controlled by dual cis regulatory elements, including a remote shadow enhancer (SE). In humans, loss of SE causes NCRNA disease, with congenital blindness due optic nerve aplasia. We generated mouse deletion model analyzed its effects on transcription, histology,...
Balancing the rate of differentiation and proliferation in developing tissues is essential to produce organs robust size composition. Although many molecular regulators have been established, how these connect physical geometrical aspects tissue architecture poorly understood. Here, using high-resolution timelapse imaging, we find that changes cell geometry associated with dense packing play a significant role regulating zebrafish neural tube. Specifically, progenitors are displaced away...
Recent expansion of duplicated genes unique in the
The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors signaling pathways have been shown to be important for RPE maintenance differentiation, but an understanding initial fate specification determination this cell type is lacking. We show that Yap/Taz-Tead activity necessary sufficient progenitors adopt identity in zebrafish. A...
Abstract In vertebrate retinal progenitor cells, the proneural factor Atoh7 exhibits a dynamic tissue and cellular expression pattern. Although resulting lineage contains all seven major cell types, only ganglion cells require for proper differentiation. Such specificity necessitates complex regulation of transcription during retina development. The Notch signaling pathway is an evolutionarily conserved suppressor bHLH expression. Previous in vivo mouse genetic studies established autonomous...
Interkinetic nuclear migration (IKNM) is the process in which pseudostratified epithelial nuclei oscillate from apical to basal surface and phase with mitotic cycle. In zebrafish retina, neuroepithelial retinal progenitor cells (RPCs) increase Notch activity movement of nuclei, depth correlates probability that next cell division will be neurogenic. This study focuses on mechanisms underlying relationships between IKNM, signaling, neurogenesis. particular, we have explored role IKNM has...
Vertebrate eye formation requires coordinated inductive interactions between different embryonic tissue layers, first described in amphibians. A network of transcription factors and signaling molecules controls these steps, with mutations causing severe ocular, neuronal, craniofacial defects. In eyeless mutant axolotls, morphogenesis arrests at the optic vesicle stage, before lens induction, development ventral forebrain structures is disrupted.We identified a 5-bp deletion rax (retina...
Abstract The Hippo pathway and its nuclear effector Yap regulate organ size cancer formation. While many modulators of activity have been identified, little is known about the target genes that mediate these growth effects. Here, we show yap -/- mutant zebrafish exhibit defects in hepatic progenitor potential liver due to impaired glucose transport nucleotide biosynthesis: transcriptomic metabolomic analyses reveal regulates expression transporter glut1 , causing decreased uptake use for...
Abstract Balancing the rate of differentiation and proliferation in developing tissues is essential to produce organs robust size composition. Whilst many molecular regulators have been established, how these connect physical geometrical aspects tissue architecture poorly understood. Here, using high-resolution timelapse imaging, we find that dense packing complex cell geometries play a significant role regulating zebrafish neural tube. Specifically, regions high density, progenitors are...