During animal development, the spatiotemporal properties of molecular events largely determine the biological outcomes. Conventional gene analysis methods lack the spatiotemporal resolution for precise dissection of developmental mechanisms. Although optogenetic tools exist for manipulating designer proteins in cultured cells, few have been successfully applied to endogenous proteins in live animals.
View Article and Find Full Text PDFMethods Mol Biol
August 2024
Dendrites of neurons receive synaptic or sensory inputs and are important sites of neuronal computation. The morphological features of dendrites not only are hallmarks of the neuronal type but also largely determine a neuron's function. Thus, dendrite morphogenesis has been a subject of intensive study in neuroscience.
View Article and Find Full Text PDFAnimal development involves numerous molecular events, whose spatiotemporal properties largely determine the biological outcomes. Conventional methods for studying gene function lack the necessary spatiotemporal resolution for precise dissection of developmental mechanisms. Optogenetic approaches are powerful alternatives, but most existing tools rely on exogenous designer proteins that produce narrow outputs and cannot be applied to diverse or endogenous proteins.
View Article and Find Full Text PDFProstaglandin (PG) D, a commonly considered vasodilator through D prostanoid receptor-1 (DP1), might also evoke vasoconstriction via acting on the thromboxane (Tx)-prostanoid receptor (the original receptor of TxA; TP) and/or E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE; EP3). This study aimed to test the above hypothesis in the mouse renal vascular bed (main renal arteries and perfused kidneys) and/or mesenteric resistance arteries and determine how the vasoconstrictor mechanism influences the overall PGD effect on systemic blood pressure under in vivo conditions. Experiments were performed on control wild-type (WT) mice and mice with deficiencies in TP (TP) and/or EP3 (EP3).
View Article and Find Full Text PDFClustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 provides a highly efficient and flexible genome editing technology with numerous potential applications ranging from gene therapy to population control. Some proposed applications involve the integration of CRISPR/Cas9 endonucleases into an organism's genome, which raises questions about potentially harmful effects to the transgenic individuals. One example for which this is particularly relevant are CRISPR-based gene drives conceived for the genetic alteration of entire populations.
View Article and Find Full Text PDFNecroinflammation plays an important role in disease settings such as acute kidney injury (AKI). We and others have elucidated that prostaglandins, which are critically involved in inflammation, may activate E-prostanoid 3 receptor (EP3) at low concentrations. However, how EP3 blockade interacts with regulated cell death and affects AKI remains unknown.
View Article and Find Full Text PDFThe F prostanoid receptor (FP), which accounts for the therapeutic effect of PGF in uterine atony that leads to postpartum hemorrhage and maternal morbidity, could possibly mediate vasoconstrictor effect in small or resistance arteries to elevate blood pressure that limits the clinical use of the agent in patients with cardiovascular disorders. This study aimed to test the above hypothesis with genetically altered mice. Ex vivo and in vivo experiments were performed on control wild-type (WT) mice and mice with deficiencies in FP (FP ) or thromboxane (Tx)-prostanoid receptor (the original receptor of TxA ; TP ), and/or those with an additional deficiency in E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE ; EP3 ).
View Article and Find Full Text PDFCRISPR/Cas9 has emerged as a powerful technology for tissue-specific mutagenesis. However, tissue-specific CRISPR/Cas9 tools currently available in remain deficient in three significant ways. First, many existing gRNAs are inefficient, such that further improvements of gRNA expression constructs are needed for more efficient and predictable mutagenesis in both somatic and germline tissues.
View Article and Find Full Text PDFVasomotor reactions of prostacyclin (prostaglandin I ; PGI ) can be collectively modulated by thromboxane prostanoid receptor (TP), E-prostanoid receptor-3 (EP3), and the vasodilator I prostanoid receptor (IP). This study aimed to determine the direct effect of PGI on renal arteries and/or the whole renal vasculature and how each of these receptors is involved. Experiments were performed on vessels or perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP ) and/or EP3.
View Article and Find Full Text PDFDuring prolonged nutrient restriction, developing animals redistribute vital nutrients to favor brain growth at the expense of other organs. In , such brain sparing relies on a glia-derived growth factor to sustain proliferation of neural stem cells. However, whether other aspects of neural development are also spared under nutrient restriction is unknown.
View Article and Find Full Text PDFAlthough recognized to have an in vivo vasodepressor effect blunted by the vasoconstrictor effect of E-prostanoid receptor-3 (EP3), prostaglandin E (PGE ) evokes contractions of many vascular beds that are sensitive to antagonizing the thromboxane prostanoid receptor (TP). This study aimed to determine the direct effect of PGE on renal arteries and/or the whole renal vasculature and how each of these two receptors is involved in the responses. Experiments were performed on isolated vessels and perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP ), EP3 (EP3 ), or both TP and EP3 (TP /EP3 ).
View Article and Find Full Text PDFEndothelial dysfunction, which leads to ischemic events under atherosclerotic conditions, can be attenuated by antagonizing the thromboxane-prostanoid receptor (TP) that mediates the vasoconstrictor effect of prostanoids including prostacyclin (PGI). This study aimed to determine whether antagonizing the E prostanoid receptor-3 (EP3; which can also be activated by PGI) adds to the above effect of TP deficiency (TP) under atherosclerotic conditions and if so, the underlying mechanism(s). Atherosclerosis was induced in ApoE mice and those with ApoE and TP.
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