A5050037409- Reproductive Biology and Fertility
- Connexins and lens biology
- Heat shock proteins research
- Ovarian function and disorders
- Sperm and Testicular Function
- Tissue Engineering and Regenerative Medicine
- Marine Invertebrate Physiology and Ecology
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
- Phosphodiesterase function and regulation
- Yersinia bacterium, plague, ectoparasites research
- Electrospun Nanofibers in Biomedical Applications
- Developmental Biology and Gene Regulation
- Bone Metabolism and Diseases
- Marine Ecology and Invasive Species
- Plant Reproductive Biology
- Regulation of Appetite and Obesity
- TGF-β signaling in diseases
- Connective Tissue Growth Factor Research
- Redox biology and oxidative stress
- Vibrio bacteria research studies
- Preterm Birth and Chorioamnionitis
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Birth, Development, and Health
- Infectious Aortic and Vascular Conditions
UConn Health
2010-2025
Rockefeller University
2024
Rockefeller University Press
2024
University of Connecticut
2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2011-2015
Children’s Health Research Institute
2012
Fred Hutch Cancer Center
2012
Western University
2012
Mammalian oocytes are arrested in meiotic prophase by an inhibitory signal from the surrounding somatic cells ovarian follicle. In response to luteinizing hormone (LH), which binds receptors on cells, oocyte proceeds second metaphase, where it can be fertilized. Here we investigate how regulate prophase-to-metaphase transition oocyte, and show that is cGMP. Using FRET-based cyclic nucleotide sensors follicle-enclosed mouse oocytes, find cGMP passes through gap junctions into oocyte,where...
Luteinizing hormone (LH) acts on ovarian follicles to reinitiate meiosis in prophase-arrested mammalian oocytes, and this has been proposed occur by interruption of a meioisis-inhibitory signal that is transmitted through gap junctions into the oocyte from somatic cells surround it. To investigate idea, we microinjected fluorescent tracers live antral follicle-enclosed mouse demonstrate for first time LH causes decrease junction permeability between cells, prior nuclear envelope breakdown...
Significance By imaging cyclic GMP (cGMP) in live ovarian follicles from mice, we show how luteinizing hormone signaling the follicle periphery results a rapid decrease cGMP oocyte, thus reinitiating meiosis. Luteinizing lowers outer cells of follicle, then oocyte decreases as consequence diffusion through gap junctions. These findings demonstrate directly that physiological signal initiated by stimulus one region an intact tissue can travel across many layers via nucleotide
The meiotic cell cycle in mouse oocytes is arrested prophase, and then restarted when LH acts on the surrounding granulosa cells. cells keep meiosis by providing a source of cGMP that diffuses into oocyte through gap junctions, restarts closing junctions decreasing cGMP, thus lowering cGMP. Epidermal growth factor receptor (EGFR) activation an essential step triggering LH-induced resumption, but its relationship to decrease follicle incompletely understood, possible function causing junction...
The Wnt family of secreted proteins has been proposed to play a conserved role in early specification the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well planarian regeneration and homeostasis, indicating that canonical (cWnt) signaling endows cells with positional information along A/P Outside these phyla, there strong support for cWnt repression anterior fates, but little comparative promotion posterior fates. We...
Abstract Intercellular organelle transfer has been documented in several cell types and proposed to be important for cell‐cell communication cellular repair. However, the mechanisms by which occurs are uncertain. Recent studies indicate that gap junction protein, connexin 43 (Cx43), is required mitochondrial but its specific role unknown. Using three‐dimensional electron microscopy immunogold labeling of Cx43, this report shows whole organelles including mitochondria endosomes incorporated...
The arrest of meiotic prophase in mouse oocytes within antral follicles requires the G protein Gs and an orphan member protein–coupled receptor family, GPR3. To determine whether GPR3 activates Gs, localization Gαs follicle-enclosed from Gpr3+/+ Gpr3−/− mice was compared by using immunofluorescence GαsGFP. decreased ratio oocyte plasma membrane versus cytoplasm also amount oocyte. Both these properties indicate that Gs. follicle cells around are necessary to keep prophase, suggesting they...
Skin homeostasis is maintained by stem cells, which must communicate to balance their regenerative behaviors. Yet, how adult cells signal across tissue remains unknown due challenges in studying signaling dynamics live mice. We combined imaging the mouse basal cell layer with machine learning tools analyze patterns of Ca2+ signaling. show that display dynamic intercellular among local neighborhoods. find these signals are coordinated thousands and this coordination an emergent property...
FGFs act in vertebrate mesoderm induction and also play key roles early formation ascidians amphioxus. However, sea urchins initial characterizations of FGF function do not support a role induction, making the ancestral signaling mechanisms specification deuterostomes unclear. In order to better characterize evolution formation, we have examined during development Saccoglossus kowalevskii, an experimentally tractable representative hemichordates. We report expression ligand, fgf8/17/18,...
Abstract Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring long bones. Many patients with suffer from neurological symptoms. The pathogenesis not fully understood. Treatment limited to surgery. Here, we report knock (KI) mouse model for AR carrying Cx43 R239Q mutation. KI/KI mice replicate typical features CMD, including thickening...
Gap junction turnover occurs through the internalization of both plasma membranes a gap plaque, forming double membrane-enclosed vesicle, or connexosome. Phosphorylation has key role in regulation, but further progress requires ability to clearly distinguish junctions and connexosomes, precisely identify proteins associated with them. We examined, by using electron microscopy, serial sections mouse preovulatory ovarian follicles that had been collected an automated tape collecting...
Gap junctions have well-established roles in cell-cell communication by way of forming permeable intercellular channels. Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell called connexosomes or annular gap junctions. Here, we systematically investigated the fate intact ovarian follicles. High-pressure frozen, serial-sectioned tissue was immunogold labeled for connexin 43 (Cx43, also known as GJA1). Within a...
Abstract Signaling in the granulosa cells of mammalian ovarian follicles is necessary for maintaining prophase arrest oocyte and mediating resumption meiosis response to luteinizing hormone (LH). However, follicle also includes an outer layer theca cells, some which express receptors LH. To investigate whether are required meiotic reinitiating LH, we mechanically separated from basal lamina. This was accomplished by cutting a slit surface isolated such that mural cumulus-oocyte complex were...
Connexin43 (CX43) forms gap junction channels that metabolically couple the granulosa cells of developing ovarian follicles. Research with knockout mice has demonstrated a requirement for this connexin in supporting follicle growth: CX43 null mutant follicles fail to develop beyond primary stage on C57BL/6 background due failure proliferate. We have used mouse line and recombinant-reaggregated ovary technique examine importance specific phosphorylation sites growth. Serines at 255, 262, 279...
Abstract Implanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), form of chronic inflammation resulting the inflammatory reaction persistent stimulus. The FBR is characterized by subset multinucleated giant cells (MGCs) formed macrophage fusion, (FBGCs), accompanied cytokines, matrix deposition, eventually deleterious fibrotic implant encapsulation. Despite efforts improve biocompatibility,...
Abstract In the Drosophila testis, developing germ cells are encapsulated by somatic support throughout development. Soma-germline interactions essential for successful spermiogenesis. However, it is still not fully understood what signaling events take place between soma and germline. this study, we found that a Bone Morphogenetic Protein (BMP) ligand, Glass bottom boat (Gbb), secreted from cyst (CCs), signals to differentiating maintain proper Knockdown of Gbb in CCs or type I BMP receptor...
Abstract Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and flaring metaphyses long bones. Many patients with suffer from neurological symptoms. To date, the pathogenesis not fully understood. Treatment limited to decompression surgery. Here, we report knock (KI) mouse model for AR carrying R239Q mutation CX43. Cx43 KI/KI mice replicate many features In...