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Loss of cell adhesion causes hydrocephalus in nonmuscle myosin II-B ablated and mutated mice
, 2007
"... Ablation of nonmuscle myosin (NM) II-B in mice during embryonic development leads to marked enlargement of the cerebral ventricles and destruction of brain tissue, due to hydrocephalus. We have identified a transient mesh-like structure present at the apical border of cells lining the spinal canal o ..."
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Ablation of nonmuscle myosin (NM) II-B in mice during embryonic development leads to marked enlargement of the cerebral ventricles and destruction of brain tissue, due to hydrocephalus. We have identified a transient mesh-like structure present at the apical border of cells lining the spinal canal of mice during development. This structure, which only contains the II-B isoform of NM, also contains �-catenin and N-cadherin, consistent with a role in cell adhesion. Ablation of NM II-B or replacement of NM II-B with decreased amounts of a mutant (R709C), motor-impaired NM II-B in mice results in collapse of the mesh-like structure and loss of cell adhesion. This permits the underlying neuroepithelial cells to invade the spinal canal and obstruct cerebral spinal fluid flow. These defects in the CNS of NM II-B–ablated mice seem to be the cause of hydrocephalus. Interestingly, the mesh-like structure and patency of the spinal canal can be restored by increasing expression of the motor-impaired NM II-B, which also rescues hydrocephalus. However, the mutant isoform cannot completely rescue neuronal cell migration. These studies show that the scaffolding properties of NM II-B play an important role in cell adhesion, thereby preventing hydrocephalus during mouse brain development.
Myosin IIC: A Third Molecular Motor Driving Neuronal Dynamics
, 2007
"... Neuronal dynamics result from the integration of forces developed by molecular motors, especially conventional myosins. Myosin IIC is a recently discovered nonsarcomeric conventional myosin motor, the function of which is poorly understood, particularly in relation to the separate but coupled activi ..."
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Neuronal dynamics result from the integration of forces developed by molecular motors, especially conventional myosins. Myosin IIC is a recently discovered nonsarcomeric conventional myosin motor, the function of which is poorly understood, particularly in relation to the separate but coupled activities of its close homologues, myosins IIA and IIB, which participate in neuronal adhesion, outgrowth and retraction. To determine myosin IIC function, we have applied a comparative functional knockdown approach by using isoform-specific antisense oligodeoxyribonucleotides to deplete expression within neuronally derived cells. Myosin IIC was found to be critical for driving neuronal process outgrowth, a function that it shares with myosin IIB. Additionally, myosin IIC modulates neuronal cell adhesion, a function that it shares with myosin IIA but not myosin IIB. Consistent with this role, myosin IIC knockdown caused a concomitant decrease in paxillin-phospho-Tyr118 immunofluorescence, similar to knockdown of myosin IIA but not myosin IIB. Myosin IIC depletion also created a distinctive phenotype with increased cell body diameter, increased vacuolization, and impaired responsiveness to triggered neurite collapse by lysophosphatidic acid. This novel combination of properties suggests that myosin IIC must participate in distinctive cellular roles and reinforces our view that closely related motor isoforms drive diverse functions within neuronal cells.
unknown title
, 2013
"... Genetic analysis of novel regulators of neuronal migration in Caenorhabditis elegans: the insulin/IGF-1 signaling pathway, a chromatin-binding factor ZFP-1 (AF10) and endogenous RNAi ..."
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Genetic analysis of novel regulators of neuronal migration in Caenorhabditis elegans: the insulin/IGF-1 signaling pathway, a chromatin-binding factor ZFP-1 (AF10) and endogenous RNAi
An MYH9 Human Disease Model in Flies: site-directed mutagenesis of the Drosophila nonmuscle myosin II results in hypomorphic alleles with dominant character
, 2007
"... We investigated whether or not human disease-causing, amino acid substitutions in MYH9 could cause dominant phenotypes when introduced into the sole nonmuscle myosin II heavy chain in Drosophila melanogaster (zip/MyoII). We characterized in vivo the effects of four MYH9-like mutations in the myosin ..."
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We investigated whether or not human disease-causing, amino acid substitutions in MYH9 could cause dominant phenotypes when introduced into the sole nonmuscle myosin II heavy chain in Drosophila melanogaster (zip/MyoII). We characterized in vivo the effects of four MYH9-like mutations in the myosin rod – R1171C, D1430N, D1847K and R1939X – which occur at highly conserved residues. These engineered mutant heavy chains resulted in D. melanogaster nonmuscle myosin II with partial wild-type function. In a wild-type genetic background, mutant heavy chains were overtly recessive and hypomorphic: each was able to substitute partially for endogenous nonmuscle myosin II heavy chain in animals lacking zygotically produced heavy chain (but the penetrance of rescue was below Mendelian expectation). Moreover, each of the four mutant heavy chains exhibits dominant characteristics when expressed in a sensitized genetic background (flies heterozygous for RhoA mutations). Thus these zip/MyoII MYH9 alleles function, like certain other hypomorphic alleles, as excellent bait in screens for genetic interactors. Our conjecture is that these mutations in D. melanogaster behave comparably to their parent mutations in humans. We further characterized these
1 Function of the Neuron-Specific Alternatively Spliced Isoforms of Nonmuscle Myosin II-B During Mouse Brain Development
"... cells, facial neuron migration Abbreviations: NMHC, nonmuscle myosin heavy chain; E, embryonic day; P, postnatal day; ES cell, embryonic stem cell; PBS, phosphate buffered saline; H&E, hematoxylin and eosin; Neo r, neomycin resistance; HMM, heavy meromyosin; CSF, cerebral spinal fluid Correspond ..."
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cells, facial neuron migration Abbreviations: NMHC, nonmuscle myosin heavy chain; E, embryonic day; P, postnatal day; ES cell, embryonic stem cell; PBS, phosphate buffered saline; H&E, hematoxylin and eosin; Neo r, neomycin resistance; HMM, heavy meromyosin; CSF, cerebral spinal fluid Correspondence should be addressed to:
1 LOSS OF CELL ADHESION CAUSES HYDROCEPHALUS IN NONMUSCLE MYOSIN II-B ABLATED AND MUTATED MICE
"... Abbreviations: aPKC, atypical PKC; CSF, cerebral spinal fluid; E, embryonic day; HMM, heavy meromyosin; MLC20, regulatory myosin light chain; NM II, nonmuscle myosin II; NMHC, nonmuscle myosin heavy chain; P, postnatal day. Please address correspondence to: ..."
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Abbreviations: aPKC, atypical PKC; CSF, cerebral spinal fluid; E, embryonic day; HMM, heavy meromyosin; MLC20, regulatory myosin light chain; NM II, nonmuscle myosin II; NMHC, nonmuscle myosin heavy chain; P, postnatal day. Please address correspondence to:
unknown title
, 2007
"... An MYH9 human disease model in flies: site-directed mutagenesis of the Drosophila non-muscle myosin II results in hypomorphic alleles with dominant character ..."
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An MYH9 human disease model in flies: site-directed mutagenesis of the Drosophila non-muscle myosin II results in hypomorphic alleles with dominant character
Function of the Neuron-specific Alternatively Spliced Isoforms of Nonmuscle Myosin II-B during Mouse
, 2005
"... We report that the alternatively spliced isoforms of nonmuscle myosin heavy chain II-B (NHMC II-B) play distinct roles during mouse brain development. The B1-inserted isoform of NMHC II-B, which contains an insert of 10 amino acids near the ATP-binding region (loop 1) of the myosin heavy chain, is i ..."
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We report that the alternatively spliced isoforms of nonmuscle myosin heavy chain II-B (NHMC II-B) play distinct roles during mouse brain development. The B1-inserted isoform of NMHC II-B, which contains an insert of 10 amino acids near the ATP-binding region (loop 1) of the myosin heavy chain, is involved in normal migration of facial neurons. In contrast, the B2-inserted isoform, which contains an insert of 21 amino acids near the actin-binding region (loop 2), is important for postnatal development of cerebellar Purkinje cells. Deletion of the B1 alternative exon, together with reduced expression of myosin II-B, results in abnormal migration and consequent protrusion of facial neurons into the fourth ventricle. This protrusion is associated with the development of hydrocephalus. Restoring the amount of myosin II-B expression to wild-type levels prevents these defects, showing the importance of total myosin activity in facial neuron migration. In contrast, deletion of the B2 alternative exon results in abnormal development of cerebellar Purkinje cells. Cells lacking the B2-inserted isoform show reduced numbers of dendritic spines and branches. Some of the B2-ablated Purkinje cells are misplaced in the cerebellar molecular layer. All of the B2-ablated mice demonstrated impaired motor coordination.
En vue de l’obtention du grade de
, 2013
"... Sujet de la Thèse: Rôle des microtubules et de l’acto-myosine dans la migration des interneurones corticaux Soutenue le 27 Mars 2008 devant le jury composé de: ..."
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Sujet de la Thèse: Rôle des microtubules et de l’acto-myosine dans la migration des interneurones corticaux Soutenue le 27 Mars 2008 devant le jury composé de:
JCB: REPORT Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells
"... We have used isoform-specifi c RNA interference knockdowns to investigate the roles of myosin IIA (MIIA) and MIIB in the component processes that drive cell migration. Both isoforms reside outside of protrusions and act at a distance to regulate cell protrusion, signaling, and maturation of nascent ..."
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We have used isoform-specifi c RNA interference knockdowns to investigate the roles of myosin IIA (MIIA) and MIIB in the component processes that drive cell migration. Both isoforms reside outside of protrusions and act at a distance to regulate cell protrusion, signaling, and maturation of nascent adhesions. MIIA also controls the dynamics and size of adhesions in central regions of the cell and contributes to retraction and adhesion disassembly at the rear. In contrast, MIIB establishes front–back polarity and
