1.Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice.
Xue LI ; Shimin ZOU ; Xiaomeng TU ; Shishuai HAO ; Tian JIANG ; Jie-Guang CHEN
Neuroscience Bulletin 2023;39(7):1131-1145
Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
Mice
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Animals
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Ependymoglial Cells/physiology*
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Cadherins
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Neurons/metabolism*
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Cerebral Cortex/metabolism*
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Cell Differentiation
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Cell Movement
2.Carbonic Anhyd rase Activity in Muller Cell.
Journal of the Korean Ophthalmological Society 2000;41(5):1068-1072
Carbonic anhydrase, an enzyme catalysing the reversible hydration of carbon dioxide, is present in the Muller cells.Because the enzyme is not present in other uroretinal cells in the retina, it can be used as a marker for Muller cells.Carbonic anhydrase activity was demonstrated bnzymehistochemically in human and rabbit Muller cells to know a relation of metabolic functions and carbonic anhydrase activity.Human retinas were obtained from donor eyes.The eyes were enucleated immediately after death forenzymatic activity. In human retina, heavy staining was found in the inner nuclear layer and nerve fiber layer, moderate staining in the outer nuclear layer and weak or no staining in the plexiform layers.In rabbit retina, heavy staining was found in the nerve fiber layer and nuclear layers and weak reaction in the two plexiform layers. These findings suggest that Muller cells may participate in CO2 homeostasis mechanism of carbonic anhydrase in the retina.
Carbon Dioxide
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Carbon*
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Carbonic Anhydrases
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Ependymoglial Cells
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Homeostasis
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Humans
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Metabolism
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Nerve Fibers
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Retina
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Tissue Donors
3.BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period.
Zhenmeiyu LI ; Guoping LIU ; Lin YANG ; Mengge SUN ; Zhuangzhi ZHANG ; Zhejun XU ; Yanjing GAO ; Xin JIANG ; Zihao SU ; Xiaosu LI ; Zhengang YANG
Protein & Cell 2024;15(1):21-35
The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals
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Mice
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Humans
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Ependymoglial Cells/metabolism*
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Hedgehog Proteins/metabolism*
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Ferrets/metabolism*
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Cerebral Cortex
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Neurogenesis
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Mammals/metabolism*
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Neuroglia/metabolism*
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Bone Morphogenetic Protein 7/metabolism*
4.Effects of avastin on expression of AQP4 in Müller cells under hypoxia.
Wei CAI ; Yang CHENG ; Lina KE ; Peng ZHANG ; Guotao DENG ; Guobao LI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(4):607-612
The aim of this study was to investigate the effects of Avastin on aquaporin4 (AQP4) expression in human retinal Müller cells in vitro under hypoxia, so as to explore the mechanism of Avastin treating retinal edema. The human Müller cells were cultured using the enzymatic digestion method. Müller cells were identified under the transmission electron microscopy and by using immunofluorescence staining. By using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), the expression of AQP4 mRNA and VEGF mRNA in Müller cells cultured with 500 μmol/L CoCl(2) for 0, 3, 6, 12 and 24 h, and with 0, 100, 300, 500 and 700 μmol/L CoCl(2) for 24 h was detected. The expression of AQP4 mRNA in Müller cells cultured with 50 ng/mL exogenous vascular endothelial growth factor (VEGF) for 0, 0.5, 1, 2 and 4 h, and with 0, 25, 50 and 75 ng/mL VEGF for 24 h was detected. Amplified cDNA products of AQP4 mRNA in Müller cells cultured with 500 μmol/L CoCl(2) and 200 μg/mL Avastin for 24 h were detected. The results showed that more than 95% cells displayed positive immunofluorescence reaction. Characteristic 8-10 nm intracellular filaments could be seen in the cytoplasm under the transmission electron microscopy. In the CoCl(2) experimental groups, the expression of AQP4 mRNA and VEGF mRNA in Müller cells was increased as compared with the control group. Alteration of AQP4 mRNA and VEGF mRNA levels showed a significantly positive correlation (r (2)=0.822, P<0.05). The expression of AQP4 mRNA in Müller cells was increased by VEGF. The expression of AQP4 mRNA was significantly decreased by Avastin as compared with the control group. It is suggested that Avastin can decrease the expression of AQP4 mRNA in human Müller cells under chemical hypoxic conditions partially via VEGF path, which may be one of the mechanisms of Avastin treating retinal edema.
Antibodies, Monoclonal, Humanized
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pharmacology
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Aquaporin 4
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genetics
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metabolism
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Bevacizumab
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Cells, Cultured
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Ependymoglial Cells
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metabolism
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Gene Expression
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drug effects
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genetics
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Humans
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Hypoxia
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genetics
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metabolism