The microcephaly gene aspm is involved in brain development in zebrafish

► We identified a zebrafish aspm/mcph5 gene that is expressed in proliferating cells in the CNS during early development. ► Embryos injected with the aspm MO consistently showed a reduced head and eye size but were otherwise grossly normal, closely mimicking the known phenotypes of human microcephal...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2011-06, Vol.409 (4), p.640-644
Main Authors: Kim, Hyun-Taek, Lee, Mi-Sun, Choi, Jung-Hwa, Jung, Ju-Yeon, Ahn, Dae-Gwon, Yeo, Sang-Yeob, Choi, Dong-Kug, Kim, Cheol-Hee
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Amino Acid Sequence
Animals
APOPTOSIS
ASPM
BRAIN
Brain - embryology
CELL CYCLE
Cell Cycle Proteins - genetics
CNS
CONGENITAL DISEASES
Danio rerio
EMBRYOS
Freshwater
Gene Knockdown Techniques
GENES
Humans
MALFORMATIONS
Microcephaly
Microcephaly - genetics
Mitosis - genetics
Mitotic arrest
Molecular Sequence Data
MUTATIONS
ONTOGENESIS
Organ Size - genetics
PATIENTS
PHENOTYPE
Zebrafish
Zebrafish - embryology
Zebrafish - genetics
Zebrafish Proteins - genetics
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Summary:► We identified a zebrafish aspm/mcph5 gene that is expressed in proliferating cells in the CNS during early development. ► Embryos injected with the aspm MO consistently showed a reduced head and eye size but were otherwise grossly normal, closely mimicking the known phenotypes of human microcephaly patients. ► Knock-down of aspm causes cell cycle arrest and apoptotic cell death during early development. MCPH is a neurodevelopmental disorder characterized by a global reduction in cerebral cortical volume. Homozygous mutation of the MCPH5 gene, also known as ASPM, is the most common cause of the MCPH phenotype. To elucidate the roles of ASPM during embryonic development, the zebrafish aspm was identified, which is specifically expressed in proliferating cells in the CNS. Morpholino-mediated knock-down of aspm resulted in a significant reduction in head size. Furthermore, aspm-deficient embryos exhibited a mitotic arrest during early development. These findings suggest that the reduction in brain size in MCPH might be caused by lack of aspm function in the mitotic cell cycle and demonstrate that the zebrafish can provide a model system for congenital diseases of the human nervous system.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2011.05.056