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Journal article
Complete Loss of Ndel1 Results in Neuronal Migration Defects and Early Embryonic Lethality
Molecular and cellular biology, v 25(17), pp 7812-7827
01 Sep 2005
PMID: 16107726
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Abstract
Regulation of cytoplasmic dynein and microtubule dynamics is crucial for both mitotic cell division and neuronal migration. NDEL1 was identified as a protein interacting with LIS1, the protein product of a gene mutated in the lissencephaly. To elucidate NDEL1 function in vivo, we generated null and hypomorphic alleles of
Ndel1
in mice by targeted gene disruption.
Ndel1
−/−
mice were embryonic lethal at the peri-implantation stage like null mutants of
Lis1
and cytoplasmic dynein heavy chain. In addition,
Ndel1
−/−
blastocysts failed to grow in culture and exhibited a cell proliferation defect in inner cell mass. Although
Ndel1
+/−
mice displayed no obvious phenotypes, further reduction of NDEL1 by making null/hypomorph compound heterozygotes (
Ndel1
cko/−
) resulted in histological defects consistent with mild neuronal migration defects. Double
Lis1
cko/+
-Ndel1
+/−
mice or
Lis1
+/−
-Ndel1
+/−
mice displayed more severe neuronal migration defects than
Lis1
cko/+
-Ndel1
+/
+
mice or
Lis1
+/−
-Ndel1
+/+
mice, respectively. We demonstrated distinct abnormalities in microtubule organization and similar defects in the distribution of β-COP-positive vesicles (to assess dynein function) between
Ndel1
or
Lis1
-null MEFs, as well as similar neuronal migration defects in
Ndel1
- or
Lis1
-null granule cells. Rescue of these defects in mouse embryonic fibroblasts and granule cells by overexpressing LIS1, NDEL1, or NDE1 suggest that NDEL1, LIS1, and NDE1 act in a common pathway to regulate dynein but each has distinct roles in the regulation of microtubule organization and neuronal migration.
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Details
- Title
- Complete Loss of Ndel1 Results in Neuronal Migration Defects and Early Embryonic Lethality
- Creators
- Shinji Sasaki - Saitama Medical UniversityDaisuke Mori - Osaka City UniversityKazuhito Toyo-oka - Osaka City UniversityAmy Chen - National Human Genome Research InstituteLisa Garrett-Beal - National Human Genome Research InstituteMasami Muramatsu - Saitama Medical UniversityShuji Miyagawa - The University of OsakaNoriko Hiraiwa - RIKEN BioResource Research CenterAtsushi Yoshiki - RIKEN BioResource Research CenterAnthony Wynshaw-Boris - University of California San DiegoShinji Hirotsune - Osaka City University
- Publication Details
- Molecular and cellular biology, v 25(17), pp 7812-7827
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000231329300038
- Scopus ID
- 2-s2.0-23844559241
- Other Identifier
- 991020099949704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology