scholarly journals DIAPH3 deficiency links microtubules to mitotic errors, defective neurogenesis, and brain dysfunction

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Eva On-Chai Lau ◽  
Devid Damiani ◽  
Georges Chehade ◽  
Nuria Ruiz-Reig ◽  
Rana Saade ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mitotic Spindle ◽  
Actin Filaments ◽  
Expression Patterns ◽  
Brain Dysfunction ◽  
Contractile Ring ◽  
Cortical Malformation ◽  
Multinucleated Cells ◽  
Multipolar Spindles ◽  
Mouse Cerebral Cortex

Diaphanous (DIAPH) 3 is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and bi-polarity of the mitotic spindle. DIAPH3-deficient cells display disorganized cytoskeleton, and multipolar spindles. DIAPH3-deficiency disrupts the expression and/or stability of several proteins including the kinetochore-associated protein SPAG5. DIAPH3 and SPAG5 have similar expression patterns in the developing brain and overlapping subcellular localization during mitosis. Knockdown of SPAG5 phenocopies the DIAPH3 deficiency, whereas its overexpression rescues the DIAHP3 knockdown phenotype. Conditional inactivation of Diaph3 in mouse cerebral cortex profoundly disrupts neurogenesis depleting cortical progenitors and neurons; and leading to cortical malformation and autistic-like behavior. Our data uncover uncharacterized functions of DIAPH3 and provide evidence that this protein belongs to a molecular toolbox that links microtubule dynamics during mitosis to aneuploidy, cell death, fate determination defects, and cortical malformation.

scholarly journals DIAPH3 deficiency links microtubules to mitotic errors, defective neurogenesis, and brain dysfunction

2020 ◽  
Author(s):  
Eva On-Chai Lau ◽  
Devid Damiani ◽  
Yves Jossin ◽  
Georges Chehade ◽  
Olivier Schakman ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Actin Filaments ◽  
Expression Patterns ◽  
Brain Dysfunction ◽  
Contractile Ring ◽  
Cortical Malformation ◽  
Microtubule Associated Proteins ◽  
Multinucleated Cells ◽  
Multipolar Spindles ◽  
Associated Proteins

AbstractDiaphanous (DIAPH) 3 is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and polarity of the mitotic spindle. DIAPH3-deficient cells display disorganized cytoskeleton, multipolar spindles, and supernumerary centrosomes. DIAPH3-deficiency disrupts the expression and/or stability of microtubule-associated proteins SPAG5 and KNSTRN. SPAG5 and DIAPH3 have similar expression patterns in the developing brain and overlapping subcellular localization during mitosis. Knockdown of SPAG5 phenocopies the DIAPH3 deficiency, whereas its overexpression rescues the DIAH3 phenotype. Conditional inactivation of Diaph3 in the cerebral cortex profoundly disrupts neurogenesis depleting cortical progenitors and neurons; and leading to cortical malformation and autistic-like behavior. Our data uncover uncharacterized functions of DIAPH3 and provide evidence that this protein belongs to a molecular toolbox that links microtubule dynamics during mitosis to aneuploidy, cell death, fate determination defects, and cortical malformation.

scholarly journals Macromolecule biosynthesis: a key function of sleep

2007 ◽  
Vol 31 (3) ◽  
pp. 441-457 ◽  
Author(s):  
Miroslaw Mackiewicz ◽  
Keith R. Shockley ◽  
Micah A. Romer ◽  
Raymond J. Galante ◽  
John E. Zimmerman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Sleep Deprivation ◽  
Expression Patterns ◽  
State Level ◽  
Altered Expression ◽  
Mouse Cerebral Cortex ◽  
Genes Encoding ◽  
Function Of Sleep ◽  
Cellular Components

The function(s) of sleep remains a major unanswered question in biology. We assessed changes in gene expression in the mouse cerebral cortex and hypothalamus following different durations of sleep and periods of sleep deprivation. There were significant differences in gene expression between behavioral states; we identified 3,988 genes in the cerebral cortex and 823 genes in the hypothalamus with altered expression patterns between sleep and sleep deprivation. Changes in the steady-state level of transcripts for various genes are remarkably common during sleep, as 2,090 genes in the cerebral cortex and 409 genes in the hypothalamus were defined as sleep specific and changed (increased or decreased) their expression during sleep. The largest categories of overrepresented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, during sleep there was upregulation of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also upregulation during sleep of genes involved in synthesis of proteins, heme, and maintenance of vesicle pools, as well as antioxidant enzymes and genes encoding proteins of energy-regulating pathways. We postulate that during sleep there is a rebuilding of multiple key cellular components in preparation for subsequent wakefulness.

Chronic Administration of Statins Alters Multiple Gene Expression Patterns in Mouse Cerebral Cortex

2004 ◽  
Vol 312 (2) ◽  
pp. 786-793 ◽  
Author(s):  
Leslie N. Johnson-Anuna ◽  
Gunter P. Eckert ◽  
Jan H. Keller ◽  
Urule Igbavboa ◽  
Cornelia Franke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Expression Patterns ◽  
Chronic Administration ◽  
Gene Expression Patterns ◽  
Multiple Gene ◽  
Mouse Cerebral Cortex

Modulated polarization microscopy displays the dynamics of cytoskeletal structures in living, motile cells

1995 ◽  
Vol 53 ◽  
pp. 902-903
Author(s):  
J. R. Kuhn ◽  
M. Poenie
Keyword(s):  
Mitotic Spindle ◽  
Actin Filaments ◽  
Cell Shape ◽  
Dynamic Structure ◽  
Living Cells ◽  
Cytoskeletal Proteins ◽  
Polarization Microscopy ◽  
Video Enhancement ◽  
Ultrastructural Studies ◽  
Motile Cells

Cell shape and movement are controlled by elements of the cytoskeleton including actin filaments an microtubules. Unfortunately, it is difficult to visualize the cytoskeleton in living cells and hence follow it dynamics. Immunofluorescence and ultrastructural studies of fixed cells while providing clear images of the cytoskeleton, give only a static picture of this dynamic structure. Microinjection of fluorescently Is beled cytoskeletal proteins has proved useful as a way to follow some cytoskeletal events, but long terry studies are generally limited by the bleaching of fluorophores and presence of unassembled monomers.Polarization microscopy has the potential for visualizing the cytoskeleton. Although at present, it ha mainly been used for visualizing the mitotic spindle. Polarization microscopy is attractive in that it pro vides a way to selectively image structures such as cytoskeletal filaments that are birefringent. By combing ing standard polarization microscopy with video enhancement techniques it has been possible to image single filaments. In this case, however, filament intensity depends on the orientation of the polarizer and analyzer with respect to the specimen.

C-fos, ERK1/2, MAP2, NOTCH1 Proteins Expression Patterns in Human Cerebral Cortex Neurons after Ischemic Stroke

2020 ◽  
Vol 75 (3) ◽  
pp. 226-233
Author(s):  
Svetlana P. Sergeeva ◽  
Aleksey V. Lyundup ◽  
Valery V. Beregovykh ◽  
Petr F. Litvitskiy ◽  
Aleksey A. Savin ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Ischemic Stroke ◽  
Expression Patterns ◽  
Immunohistochemical Method ◽  
Left Middle Cerebral Artery ◽  
Contralateral Hemisphere ◽  
Human Cerebral Cortex ◽  
Fos Protein ◽  
Urgent Task ◽  
Indirect Immunoperoxidase

Background. The search for protein (these include c-fos, ERK1/2, MAP2, NOTCH1) expression that provide neuroplasticity mechanisms of the cerebral cortex after ischemic stroke (IS) patterns is an urgent task. Aims to reveal c-fos, ERK1/2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after IS. Materials and methods. We studied 9 left middle cerebral artery (LMCA) IS patients cerebral cortex samples from 3 zones: 1 the zone adjacent to the necrotic tissue focus; 2 zone remote from the previous one by 47 cm; 3 zone of the contralateral hemisphere, symmetric to the IS focus. Control samples were obtained from 3 accident died people. Identification of targeted proteins NSE, c-fos, ERK1/2, MAP2, NOTCH1 was performed by indirect immunoperoxidase immunohistochemical method. Results. Moving away from the ischemic focus, there is an increase in the density of neurons and a decrease in the damaged neurons proportion, the largest share of c-fos protein positive neurons in zone 2, NOTCH1 positive neurons in zone 1, smaller fractions of ERK1/2 and MAP2 positive neurons compared to the control only in samples of zone 1. Conclusions. With the IS development, the contralateral hemisphere is intact tissue increased activation zone, while the zones 1 and 2 have pathological activation signs. In zone 1 of the range, the adaptive response of the tissue decreases, and in zone 2 it expands. Therefore, a key target for therapeutic intervention is zone 2.

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