Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development.

Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Research Abstract Details 

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Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Abstract Text:

A Wynshaw-Boris,

Lissencephaly is a severe human neuronal migration defect characterized by a smooth cerebral surface, mental retardation and seizures. LIS1 was first gene cloned in an organism important for neuronal migration, as it was deleted or mutated in patients with lissencephaly in a heterozygous fashion. Studies in model organisms, particularly Aspergillus nidulans, as well as those in the mouse, have uncovered an evolutionarily conserved pathway that involves LIS1 and cytoplasmic dynein. This pathway codes for proteins in a complex with cytoplasmic dynein and positively regulates its conserved function in nuclear migration. This complex appears to be important for proliferation and neuronal survival as well as neuronal migration. One of the components of this complex, NDEL1, is a phosphoprotein that is a substrate for CDK5 (or CDK2 in fibroblasts) and Aurora-A, two mitotic kinases. CDK5-phosphorylated NDEL1 binds to 14-3-3epsilon, which protects it from phosphatase attack. Interestingly, 14-3-3epsilon is located 1 Mb from LIS1 and is heterozygously deleted with LIS1 in patients with a severe form of lissencephaly, Miller-Dieker syndrome. Mouse models confirm that 14-3-3epsilon plays an important role in neuronal migration, and mice that are double heterozygotes for mutations in Lis1 and 14-3-3epsilon, display more severe neuronal migration defects. The identification of LIS1 as the first lissencephaly gene, and the first gene required for neuronal migration has revealed the importance of the regulation of cytoplasmic dynein in the control of neuronal migration by modulating nuclear migration in a pathway conserved in virtually all eukaryotes.

Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Publishing Authors By Initials

A Wynshaw-Boris,

For similar cells: stem cells research abstracts see: cells: stem cells research

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Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Journal Published:

PUBLICATION TYPE: Review

Journal: Clinical genetics

VOLUME: 72

Page Numbers: 296-304

Journal Abbreviation: Clin. Genet.

ISSN: 0009-9163

DAY: 3

MONTH: Oct

YEAR: 2007

Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Information

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LANGUAGE: eng

NlmUniqueID: 253664

Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Keywords Mesh Terms:

KEYWORDS: Stem Cells

MESH TERMS: metabolism

Chemical & Substance for Abstract: Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Information

Substance Name: PAFAH1B1 protein, human

Registry Number: EC 3.1.1.47

Grant and Affiliation Information for Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development.

AFFILIATION: Departments of Pediatrics and Medicine, UCSD School of Medicine, University of California-San Diego, La Jolla, CA, USA. awynshawboris@ucsd.edu

Country: Denmark

AGENCY: United States NINDS

GRANT: NS 41030

ACRONYM: NS

MEDLINETA: Clin Genet

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