Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease

During cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions...

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Main Author: Volney L. Sheen
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Scientifica
Online Access:http://dx.doi.org/10.6064/2012/480129
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author Volney L. Sheen
author_facet Volney L. Sheen
author_sort Volney L. Sheen
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description During cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions and consequent expansion of the progenitor pool, as well as impact the integrity of the neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial scaffolding and alters initial neuronal migration from the ventricular zone. Vesicle trafficking is also required for maintenance of lipid and protein cycling within the leading and trailing edge of migratory neurons, as well as dendrites and synapses of mature neurons. Defects in this transport machinery disrupt neuronal identity, migration, and connectivity and give rise to a malformation of cortical development termed as periventricular heterotopia (PH). PH is characterized by a reduction in brain size, ectopic clusters of neurons localized along the lateral ventricle, and epilepsy and dyslexia. These anatomical anomalies correlate with developmental impairments in neural progenitor proliferation and specification, migration from loss of neuroependymal integrity and neuronal motility, and aberrant neuronal process extension. Genes causal for PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network. This paper explores the role of these dynamic processes in cortical development and disease.
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spelling doaj-art-8a3d38cb67014bbc9b311dff0a7ab47e2025-08-20T03:37:50ZengWileyScientifica2090-908X2012-01-01201210.6064/2012/480129480129Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and DiseaseVolney L. Sheen0Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USADuring cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions and consequent expansion of the progenitor pool, as well as impact the integrity of the neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial scaffolding and alters initial neuronal migration from the ventricular zone. Vesicle trafficking is also required for maintenance of lipid and protein cycling within the leading and trailing edge of migratory neurons, as well as dendrites and synapses of mature neurons. Defects in this transport machinery disrupt neuronal identity, migration, and connectivity and give rise to a malformation of cortical development termed as periventricular heterotopia (PH). PH is characterized by a reduction in brain size, ectopic clusters of neurons localized along the lateral ventricle, and epilepsy and dyslexia. These anatomical anomalies correlate with developmental impairments in neural progenitor proliferation and specification, migration from loss of neuroependymal integrity and neuronal motility, and aberrant neuronal process extension. Genes causal for PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network. This paper explores the role of these dynamic processes in cortical development and disease.http://dx.doi.org/10.6064/2012/480129
spellingShingle Volney L. Sheen
Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease
Scientifica
title Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease
title_full Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease
title_fullStr Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease
title_full_unstemmed Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease
title_short Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease
title_sort periventricular heterotopia shuttling of proteins through vesicles and actin in cortical development and disease
url http://dx.doi.org/10.6064/2012/480129
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