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09:25
Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex
Published on: June 4, 2014
The exon junction complex component Magoh controls brain size by regulating neural stem cell division.
Debra L Silver1, Dawn E Watkins-Chow, Karisa C Schreck
1Genetic Disease Research Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Nature Neuroscience
|April 6, 2010
Summary
Magoh, an RNA-binding protein component of the exon junction complex (EJC), is crucial for regulating neural stem cell division and mouse brain size. Its deficiency leads to microcephaly by disrupting mitosis and neuronal development.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Precise neural stem cell (NSC) division is essential for brain development.
- Factors regulating NSCs and the mechanisms behind microcephaly are not fully understood.
Purpose of the Study:
- To investigate the role of Magoh, an exon junction complex (EJC) component, in regulating mouse cerebral cortical size.
- To elucidate the mechanisms by which Magoh deficiency causes microcephaly.
Main Methods:
- Studied Magoh haploinsufficiency in mice.
- Analyzed neural stem cell division, intermediate neural progenitor (INP) generation, and neuronal apoptosis.
- Investigated mitotic spindle integrity, chromosome number, and genomic stability.
- Performed in utero rescue experiments to assess Magoh's function in neurogenesis.
Main Results:
- Magoh haploinsufficiency resulted in microcephaly due to INP depletion and neuronal apoptosis.
- EJC component depletion disrupted mitosis, affecting spindle orientation, chromosome number, and genomic stability.
- Magoh is essential for controlling Lis1 protein levels during neurogenesis.
Conclusions:
- The exon junction complex (EJC) is required for proper brain development, NSC maintenance, and mitosis.
- Magoh plays a critical role in regulating cerebral cortical size.
- Defects in Magoh and the EJC are implicated in the pathogenesis of microcephaly.
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