A5082328350- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Protist diversity and phylogeny
- Corneal Surgery and Treatments
- Parasite Biology and Host Interactions
- Ocular Surface and Contact Lens
- Microtubule and mitosis dynamics
- Sperm and Testicular Function
- Epigenetics and DNA Methylation
- Renal and related cancers
- Micro and Nano Robotics
- melanin and skin pigmentation
- Photosynthetic Processes and Mechanisms
- Connective tissue disorders research
- Planarian Biology and Electrostimulation
- Marine Ecology and Invasive Species
- Glaucoma and retinal disorders
- Biomedical Research and Pathophysiology
- Assisted Reproductive Technology and Twin Pregnancy
- Polyamine Metabolism and Applications
- Retinal and Macular Surgery
- Congenital Ear and Nasal Anomalies
- Corneal surgery and disorders
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
Johns Hopkins Medicine
2019-2025
Johns Hopkins University
2019-2025
Icahn School of Medicine at Mount Sinai
2004-2019
Allen Institute for Brain Science
2014-2018
Washington University in St. Louis
2006-2009
Centre National de la Recherche Scientifique
1994-1998
Muséum national d'Histoire naturelle
1997
University of Milan
1994
We used an improved procedure to analyze the intraflagellar transport (IFT) of protein particles in Chlamydomonas and found that frequency particles, not only velocity, changes at each end flagella. Thus, undergo structural remodeling both flagellar locations. Therefore, we propose IFT consists a cycle composed least four phases: phases II IV, which anterograde retrograde transport, respectively, I III, are remodeled/exchanged proximal distal flagellum, respectively. In support our model,...
We identified primary cilia and centrosomes in cultured human umbilical vein endothelial cells (HUVEC) by antibodies to acetyl-α-tubulin capillary morphogenesis gene-1 product (CMG-1), a homologue of the intraflagellar transport (IFT) protein IFT-71 Chlamydomonas. CMG-1 was present particles along HUVEC at interphase around oldest basal body/centriole mitosis. To study response mechanical stimuli, we exposed laminar shear stress (LSS). Under LSS, all disassembled, were deprived CMG-1....
Significance This study defines a cellular mechanism by which primary cilia mediate mechanosensation in intraocular pressure regulation. Changes are sensed the interaction of inositol phosphatase OCRL with transient receptor potential vanilloid 4 (TRPV4), cilia-based calcium channel. Pediatric glaucoma (Lowe) syndrome patient cells defective failed to respond agonists TRPV4, and targeting TRPV4 lowered vivo. These findings significantly advance current understanding how is regulated.
Abstract The intraflagellar transport machinery is required for the assembly of cilia. It has been investigated by biochemical, genetic, and computational methods that have identified at least 21 proteins assemble into two subcomplexes. hypothesized complex A retrograde transport. Temperature-sensitive mutations in FLA15 FLA17 show defects (IFT) Chlamydomonas. We IFT144 IFT139, proteins, are encoded FLA17, respectively. fla15 allele a missense mutation conserved cysteine fla17 an in-frame...
Acetylation of α-tubulin on lysine 40 marks long-lived microtubules in structures such as axons and cilia, yet the physiological role K40 acetylation is elusive. Although genetic ablation acetyltransferase αTat1 mice did not lead to detectable phenotypes developing animals, contact inhibition proliferation cell-substrate adhesion were significantly compromised cultured αTat1(-/-) fibroblasts. First, fibroblasts kept proliferating beyond confluent monolayer stage. Congruently, cells failed...
Primary cilia have been linked to signaling pathways involved in cell proliferation, motility and polarity. Defects ciliary function result developmental abnormalities multiple ciliopathies. Patients affected by severe ciliopathies such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here we show that primary are predominantly on basal cells the corneal epithelium (CE) throughout development adult. Conditional ablation CE leads an increase...
Primary cilia are required for several signaling pathways, but their function in cellular morphogenesis is poorly understood. Here we show that emergence of an hexagonal pattern during development the corneal endothelium (CE), a monolayer neural crest-derived cells maintains transparency, depends on precise temporal control assembly primary subsequently disassemble adult endothelial (CECs). However, reassembly occurs rapidly response to vivo mechanical injury and precedes basal body...
To test the hypothesis that autophagy dysfunction is involved in exfoliation syndrome (XFS), a systemic disorder of extracellular elastic matrices causes distinct form human glaucoma.Fibroblasts derived from tenon tissue discards (TFs) filtration surgery to relieve intraocular pressure XFS patients were compared against age-matched TFs primary open-angle glaucoma (POAG) or strabismus surgery. Differential interference contrast light, and electron microscopy used examine structural cell...
Cilia-mediated signal transduction involves precise targeting and localization of selected molecules along the ciliary membrane. However, molecular mechanism underlying these events is unclear. The Joubert syndrome protein ARL13B a membrane-associated G-protein that localizes cilium functions in transport signaling. We identify tubulin as direct interactor demonstrate association occurs via G-domain independently from GTPase activity ARL13B. necessary for interaction with axoneme both vitro...
Wnt/Wg-signalling is critical signalling in all metazoans. Recent studies suggest that IFT-A proteins and Kinesin-2 modulate canonical independently of their ciliary role. Whether they function together Wnt-signalling mechanistic role the pathway remained unresolved. Here we demonstrate act as a complex during Drosophila Wg-signalling, affecting activity same manner, interacting genetically physically, co-localizing with β-catenin, mediator on microtubules. Following activation,...
Primary cilia have been linked to signaling pathways involved in cell proliferation, motility and polarity. Defects ciliary function result developmental abnormalities multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary are predominantly on basal cells the mouse corneal epithelium (CE) throughout development adult. Conditional ablation CE leads an...
Defects affecting tissues of the anterior segment (AS) eye lead to a group highly debilitating disorders called Anterior Segment Dysgenesis (ASD). Despite identification some causative genes, pathogenesis ASD remains unclear. Interestingly, several ciliopathies display conditions AS. Using conditional targeting Ift88 with Wnt1-Cre, we show that primary cilia neural crest cells (NCC), precursors most AS structures, are indispensable for normal development and their ablation leads including...
Purpose: The transcription factor c-Myc (Myc) plays central regulatory roles in both self-renewal and differentiation of progenitors multiple cell lineages. Here, we address its function corneal epithelium (CE) maintenance repair. Methods: Myc ablation the limbal–corneal was achieved by crossing a floxed mouse allele (Mycfl/fl) with line expressing Cre recombinase gene under keratin (Krt) 14 promoter. CE stratification protein localization were assessed histology paraffin plastic sections...
Intraflagellar transport moves proteins in and out of flagella/cilia it is essential for the assembly these organelles. Using whole-genome sequencing, we identified splice site mutations two IFT genes, IFT81 ( fla9 ) IFT121 ift121-2 ), which lead to flagellar defects unicellular green alga Chlamydomonas reinhardtii . The splicing ift mutants are partially corrected by conserved spliceosome proteins, DGR14 FRA10. We a dgr14 deletion mutant, suppresses 3′ mutation , frameshift mutant FRA10 5′...
Abstract Spermiogenesis and spermatozoa were studied by transmission scanning electron microscopy in Troglocaridicola sp., a scutariellid epizoic on cavernicolous freshwater shrimp. involves elongation of the spermatid which nucleus elongates, but remains close to common cytoplasmic mass. Flagella first grow opposite direction at right angle shaft, centrioles show associate structures. Later, two rotate flagella emerge parallel, still perpendicular shaft. An apical process elongates...
The distribution of glycylated tubulin has been analyzed in different populations stable microtubules a digenean flatworm, Echinostoma caproni (Platyhelminthes). Two cellular types, spermatozoa and ciliated excretory cells, have by means immunofluorescence, immunogold, immunoblotting techniques using two monoclonal antibodies (mAbs), AXO 49, TAP 952, specifically directed against differently isoforms tubulin. presence the cell types was shown. However, differential reactivities 952 49 mAbs...