Expression Analyses of POGZ, A Responsible Gene for Neurodevelopmental Disorders, during Mouse Brain Development

2019 ◽  
Vol 41 (1-2) ◽  
pp. 139-148 ◽  
Author(s):  
Kyoko Ibaraki ◽  
Nanako Hamada ◽  
Ikuko Iwamoto ◽  
Hidenori Ito ◽  
Noriko Kawamura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Development ◽  
Mouse Brain ◽  
Neurodevelopmental Disorders ◽  
Hippocampal Neurons ◽  
Morphological Characterization ◽  
Synaptic Function ◽  
Early Developmental Stage ◽  
Heterochromatin Protein 1 ◽  
Biochemical Fractionation

POGZ is a heterochromatin protein 1 α-binding protein and regulates gene expression. On the other hand, accumulating pieces of evidence indicate that the POGZ gene abnormalities are involved in various neurodevelopmental disorders. In this study, we prepared a specific antibody against POGZ, anti-POGZ, and carried out biochemical and morphological characterization with mouse brain tissues. Western blotting analyses revealed that POGZ is expressed strongly at embryonic day 13 and then gradually decreased throughout the brain development process. In immunohistochemical analyses, POGZ was found to be enriched in cerebrocortical and hippocampal neurons in the early developmental stage. The nuclear expression was also detected in Purkinje cells in cerebellum at postnatal day (P)7 and P15 but disappeared at P30. In primary cultured hippocampal neurons, while POGZ was distributed mainly in the nucleus, it was also visualized in axon and dendrites with partial localization at synapses in consistency with the results obtained in biochemical fractionation analyses. The obtained results suggest that POGZ takes part in the regulation of synaptic function as well as gene expression during brain development.

scholarly journals Uncovering Statistical Links Between Gene Expression and Structural Connectivity Patterns in the Mouse Brain

2021 ◽  
Author(s):  
Nestor Timonidis ◽  
Alberto Llera ◽  
Paul H. E. Tiesinga
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Structural Connectivity ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Synaptic Function ◽  
Reticular Nucleus ◽  
Sources Of Information ◽  
Independent Components ◽  
Brain Connectome

AbstractFinding links between genes and structural connectivity is of the utmost importance for unravelling the underlying mechanism of the brain connectome. In this study we identify links between the gene expression and the axonal projection density in the mouse brain, by applying a modified version of the Linked ICA method to volumetric data from the Allen Institute for Brain Science for identifying independent sources of information that link both modalities at the voxel level. We performed separate analyses on sets of projections from the visual cortex, the caudoputamen and the midbrain reticular nucleus, and we determined those brain areas, injections and genes that were most involved in independent components that link both gene expression and projection density data, while we validated their biological context through enrichment analysis. We identified representative and literature-validated cortico-midbrain and cortico-striatal projections, whose gene subsets were enriched with annotations for neuronal and synaptic function and related developmental and metabolic processes. The results were highly reproducible when including all available projections, as well as consistent with factorisations obtained using the Dictionary Learning and Sparse Coding technique. Hence, Linked ICA yielded reproducible independent components that were preserved under increasing data variance. Taken together, we have developed and validated a novel paradigm for linking gene expression and structural projection patterns in the mouse mesoconnectome, which can power future studies aiming to relate genes to brain function.

scholarly journals Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following Maternal Respiratory Viral Infection

2018 ◽  
Vol 40 (2) ◽  
pp. 104-119 ◽  
Author(s):  
Adrienne M. Antonson ◽  
Bindu Balakrishnan ◽  
Emily C. Radlowski ◽  
Geraldine Petr ◽  
Rodney W. Johnson
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Brain Development ◽  
Hippocampal Neurons ◽  
Protein A ◽  
Fetal Brain ◽  
Respiratory Syndrome Virus ◽  
Maternal Infection ◽  
Ki 67 ◽  
Fetal Brain Development

Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses were removed by cesarean section at GD 111 (3 days before anticipated parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 levels and developed transient febrile and anorectic responses lasting approximately 21 days. Despite having a similar overall body weight, fetuses from the PRRSV-infected gilts had a decreased brain weight and altered hippocampal gene expression compared to fetuses from control gilts. Notably, maternal infection caused a reduction in estimated neuronal numbers in the fetal dentate gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, but the relative integrated density of GFAP+ staining was increased, in addition to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. Maternal viral infection caused an increase in fetal hippocampal gene expression of the inflammatory cytokines TNF-α and IFN-γ and the myelination marker myelin basic protein. MHCII protein, a classic monocyte activation marker, was reduced in microglia, while expression of the MHCII gene was decreased in hippocampal tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest that maternal viral infection at the beginning of the last trimester results in a reduction in fetal hippocampal neurons that is evident 5 weeks after infection, when fetal piglets are near full term. The neuronal reduction was not accompanied by pronounced neuroinflammation at GD 111, indicating that any activation of classic neuroinflammatory pathways by maternal viral infection, if present, is mostly resolved by parturition.

scholarly journals Local translation in synaptic mitochondria influences synaptic transmission

2020 ◽  
Author(s):  
Roya Yousefi ◽  
Eugenio F. Fornasiero ◽  
Lukas Cyganek ◽  
Stefan Jakobs ◽  
Silvio O. Rizzoli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hippocampal Neurons ◽  
Spatial Organization ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Translation ◽  
Ample Evidence

ABSTRACTMitochondria possess a small genome that codes for core subunits of the oxidative phosphorylation system, and whose expression is essential for energy production. Information on the regulation and spatial organization of mitochondrial gene expression in the cellular context has been difficult to obtain. Here we addressed this by devising an imaging approach to analyze mitochondrial translation, by following the incorporation of clickable non-canonical amino acids. We applied this method to multiple cell types, including hippocampal neurons, where we found ample evidence for mitochondrial translation in both dendrites and axons. Translation levels were surprisingly heterogeneous, were typically stronger in axons, and were independent of their distance from the cell soma, where mitochondria presumably descent from. Presynaptic mitochondrial translation correlated with local synaptic activity, and blocking mitochondria translation reduced synaptic function. Overall, these findings demonstrate that mitochondrial gene expression in neurons is intimately linked to neuronal function.

scholarly journals Physiological Significance of WDR45, A Responsible Gene for β-propeller Protein Associated Neurodegeneration (BPAN), in Brain Development

2020 ◽  
Author(s):  
Mariko Noda ◽  
Hidenori Ito ◽  
Koh-ichi Nagata
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Cortical Neurons ◽  
De Novo ◽  
Early Stage ◽  
Physiological Role ◽  
Global Developmental Delay ◽  
Dependent Manner ◽  
Biochemical Fractionation ◽  
Biochemical Analyses

Abstract WDR45 plays an essential role in the early stage of autophagy. De novo heterozygous mutations in WDR45 have been known to cause b-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA). Although BPAN patients display global developmental delay including intellectual disability, neurodevelopmental pathophysiology of BPAN remains largely unknown. In the present study, we analyzed the physiological role of Wdr45 and pathophysiological significance of the gene abnormality during mouse brain development. Morphological and biochemical analyses revealed that Wdr45 is expressed in a developmental stage-dependent manner in mouse brain. Wdr45 was also found to be located in the excitatory synapses in biochemical fractionation. Since the WDR45 mutations are thought to cause protein degradation, we conducted acute knockdown experiments by an in utero electroporation method with mice to recapitulate the pathophysiological conditions of BPAN. Silencing of Wdr45 caused abnormal dendritic development and synaptogenesis during corticogenesis, both of which were significantly rescued by co-expression with RNAi-resistant version of Wdr45. In addition, terminal arbors of callosal axons were less developed in Wdr45-deficient cortical neurons of adult mouse when compared to the control cells. These results strongly suggest a pathophysiological significance of WDR45 gene abnormalities in neurodevelopmental aspects of BPAN.

Morphological characterization of mammalian Timeless in the mouse brain development

2015 ◽  
Vol 92 ◽  
pp. 21-28 ◽  
Author(s):  
Yutaka Inaguma ◽  
Hidenori Ito ◽  
Akira Hara ◽  
Ikuko Iwamoto ◽  
Ayumi Matsumoto ◽  
...  
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Morphological Characterization ◽  
Mouse Brain Development

scholarly journals Assessing the requirements of prenatal UBE3A expression for rescue of behavioral phenotypes in a mouse model for Angelman syndrome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Monica Sonzogni ◽  
Peipei Zhai ◽  
Edwin J. Mientjes ◽  
Geeske M. van Woerden ◽  
Ype Elgersma
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Brain Development ◽  
Mouse Brain ◽  
Angelman Syndrome ◽  
Neurodevelopmental Disorder ◽  
Brain Regions ◽  
Critical Function ◽  
Behavioral Phenotypes ◽  
Mouse Brain Development

Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of functional ubiquitin protein ligase E3A (UBE3A). In neurons, UBE3A expression is tightly regulated by a mechanism of imprinting which suppresses the expression of the paternal UBE3A allele. Promising treatment strategies for AS are directed at activating paternal UBE3A gene expression. However, for such strategies to be successful, it is important to know when such a treatment should start, and how much UBE3A expression is needed for normal embryonic brain development. Methods Using a conditional mouse model of AS, we further delineated the critical period for UBE3A expression during early brain development. Ube3a gene expression was induced around the second week of gestation and mouse phenotypes were assessed using a behavioral test battery. To investigate the requirements of embryonic UBE3A expression, we made use of mice in which the paternal Ube3a allele was deleted. Results We observed a full behavioral rescue of the AS mouse model phenotypes when Ube3a gene reactivation was induced around the start of the last week of mouse embryonic development. We found that full silencing of the paternal Ube3a allele was not completed till the first week after birth but that deletion of the paternal Ube3a allele had no significant effect on the assessed phenotypes. Limitations Direct translation to human is limited, as we do not precisely know how human and mouse brain development aligns over gestational time. Moreover, many of the assessed phenotypes have limited translational value, as the underlying brain regions involved in these tasks are largely unknown. Conclusions Our findings provide further important insights in the requirement of UBE3A expression during brain development. We found that loss of up to 50% of UBE3A protein during prenatal mouse brain development does not significantly impact the assessed mouse behavioral phenotypes. Together with previous findings, our results indicate that the most critical function for mouse UBE3A lies in the early postnatal period between birth and P21.

scholarly journals Physiological significance of WDR45, a responsible gene for β-propeller protein associated neurodegeneration (BPAN), in brain development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariko Noda ◽  
Hidenori Ito ◽  
Koh-ichi Nagata
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Cortical Neurons ◽  
De Novo ◽  
Early Stage ◽  
Physiological Role ◽  
Global Developmental Delay ◽  
Dependent Manner ◽  
Biochemical Fractionation ◽  
Biochemical Analyses

AbstractWDR45 plays an essential role in the early stage of autophagy. De novo heterozygous mutations in WDR45 have been known to cause β-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA). Although BPAN patients display global developmental delay with intellectual disability, the neurodevelopmental pathophysiology of BPAN remains largely unknown. In the present study, we analyzed the physiological role of Wdr45 and pathophysiological significance of the gene abnormality during mouse brain development. Morphological and biochemical analyses revealed that Wdr45 is expressed in a developmental stage-dependent manner in mouse brain. Wdr45 was also found to be located in excitatory synapses by biochemical fractionation. Since WDR45 mutations are thought to cause protein degradation, we conducted acute knockdown experiments by in utero electroporation in mice to recapitulate the pathophysiological conditions of BPAN. Knockdown of Wdr45 caused abnormal dendritic development and synaptogenesis during corticogenesis, both of which were significantly rescued by co-expression with RNAi-resistant version of Wdr45. In addition, terminal arbors of callosal axons were less developed in Wdr45-deficient cortical neurons of adult mouse when compared to control cells. These results strongly suggest a pathophysiological significance of WDR45 gene abnormalities in neurodevelopmental aspects of BPAN.

Morphological characterization of Class III phosphoinositide 3-kinase during mouse brain development

2015 ◽  
Vol 49 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yutaka Inaguma ◽  
Hidenori Ito ◽  
Ikuko Iwamoto ◽  
Ayumi Matsumoto ◽  
Takanori Yamagata ◽  
...  
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Morphological Characterization ◽  
Class Iii ◽  
Phosphoinositide 3 Kinase ◽  
Mouse Brain Development
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