Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6-locus

1993 ◽  
Vol 86 (2) ◽  
pp. 126-135 ◽  
Author(s):  
Wolfgang Schmahl ◽  
Monika Knoedlseder ◽  
Jack Favor ◽  
Duncan Davidson
Keyword(s):  
Point Mutation ◽  
Neuronal Migration ◽  
Cortical Malformations

scholarly journals Mutation of the α-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration

2017 ◽  
Vol 216 (8) ◽  
pp. 2443-2461 ◽  
Author(s):  
Richard Belvindrah ◽  
Kathiresan Natarajan ◽  
Preety Shabajee ◽  
Elodie Bruel-Jungerman ◽  
Jennifer Bernard ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Glial Cells ◽  
Neuronal Migration ◽  
Cortical Malformations ◽  
Tubulin Isotype ◽  
Modeling Data ◽  
Migratory Stream ◽  
Β Tubulin

Brain development involves extensive migration of neurons. Microtubules (MTs) are key cellular effectors of neuronal displacement that are assembled from α/β-tubulin heterodimers. Mutation of the α-tubulin isotype TUBA1A is associated with cortical malformations in humans. In this study, we provide detailed in vivo and in vitro analyses of Tuba1a mutants. In mice carrying a Tuba1a missense mutation (S140G), neurons accumulate, and glial cells are dispersed along the rostral migratory stream in postnatal and adult brains. Live imaging of Tuba1a-mutant neurons revealed slowed migration and increased neuronal branching, which correlated with directionality alterations and perturbed nucleus–centrosome (N–C) coupling. Tuba1a mutation led to increased straightness of newly polymerized MTs, and structural modeling data suggest a conformational change in the α/β-tubulin heterodimer. We show that Tuba8, another α-tubulin isotype previously associated with cortical malformations, has altered function compared with Tuba1a. Our work shows that Tuba1a plays an essential, noncompensated role in neuronal saltatory migration in vivo and highlights the importance of MT flexibility in N–C coupling and neuronal-branching regulation during neuronal migration.

scholarly journals Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0185103 ◽  
Author(s):  
Dolores González-Morón ◽  
Sebastián Vishnopolska ◽  
Damián Consalvo ◽  
Nancy Medina ◽  
Marcelo Marti ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Somatic Mutations ◽  
Molecular Defects ◽  
Cortical Malformations ◽  
Neuronal Migration Disorders ◽  
Migration Disorders

scholarly journals Functional characterization of RELN missense mutations involved in recessive and dominant forms of Neuronal Migration Disorders

2021 ◽  
Author(s):  
Martina Riva ◽  
Sofia Ferreira ◽  
Vera P. Medvedeva ◽  
Frédéric Causeret ◽  
Olivia J. Henry ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
De Novo ◽  
Functional Characterization ◽  
Valuable Insight ◽  
Embryonic Mouse ◽  
Cortical Malformations ◽  
Neuronal Migration Disorders ◽  
Migration Disorders

RELN is a large secreted glycoprotein that acts at multiple steps of cerebral cortex development, including neuronal migration. Only recessive mutations of the Reelin gene (RELN) have been associated with human cortical malformations and none has been functionally characterized. We identified novel missense RELN mutations in both compound and de novo heterozygous patients exhibiting an array of neuronal migration disorders (NMDs) as diverse as pachygyria, polymicrogyria and heterotopia. Most mutations caused defective RELN secretion in vitro and, when ectopically expressed in the embryonic mouse cortex, affected neuronal aggregation and/or migration in vivo. We determined the de novo heterozygous mutations acted as dominant negative and demonstrated that RELN mutations mediate not only recessive, but also dominant NMDs. This work assesses for the first time the pathogenicity of RELN mutations showing a strong genotype-phenotype correlation. In particular, the behavior of the mutant proteins in vitro and in vivo predicts the severity of cortical malformations and provides valuable insight into the pathogenesis of these disorders.

Paris I Dysfibrinogenemia: A Point Mutation in Intron 8 Results in Insertion of a 15 Amino Acid Sequence in the Fibrinogen γ-Chain

1993 ◽  
Vol 69 (03) ◽  
pp. 217-220 ◽  
Author(s):  
Jonathan B Rosenberg ◽  
Peter J Newman ◽  
Michael W Mosesson ◽  
Marie-Claude Guillin ◽  
David L Amrani
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Point Mutation ◽  
Genomic Dna ◽  
Comparative Sequence Analysis ◽  
Chain Gene ◽  
Molecular Defect ◽  
Nucleotide Position ◽  
Normal Individuals ◽  
Polymerase Chain

SummaryParis I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal γ-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the γ-chain region of the Paris I subject’s genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A→G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I γ-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature γparis I chain mRNA, and encodes a 15 amino acid insert after γ350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I γ-chain mRNA also results after translation into a substitution of S for G at position γ351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the γpariS I chain. We conclude that the insertion of this amino acid sequence leads to a conformationallyaltered, and dysfunctional γ-chain in Paris I fibrinogen.

EPILEPSY SURGERY FOR SYMPTOMATIC WEST SYNDROME WITH CORTICAL MALFORMATIONS

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
K Kagitani-Shimono ◽  
K Imai ◽  
T Okinaga ◽  
Y Mogami ◽  
K Araya ◽  
...  
Keyword(s):  
Epilepsy Surgery ◽  
West Syndrome ◽  
Cortical Malformations

Skeletal and bone material phenotype in recessive osteogenesis imperfecta due to a novel homozygous point mutation in TMEM38B

2015 ◽  
Author(s):  
Emma Webb ◽  
Meena Balasubramanian ◽  
Trevor Cole ◽  
Sue Stewart ◽  
Nicola Crabtree ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Point Mutation ◽  
Bone Material

Mutations in IGSF10 cause self-limited delayed puberty, via disturbance of GnRH neuronal migration

2015 ◽  
Author(s):  
Sasha Howard ◽  
Leo Guasti ◽  
Gerard Ruiz-Babot ◽  
Alessandra Mancini ◽  
Alessia David ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Delayed Puberty
Sign in / Sign up

Export Citation Format

Share Document