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ASPM regulates Wnt signaling pathway activity in the developing brain.
Joshua J Buchman1, Omer Durak, Li-Huei Tsai
1Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Genes & Development
|September 23, 2011
Summary
Abnormal Spindle Microcephaly (ASPM) gene mutations cause primary microcephaly, a brain development disorder. Our study shows ASPM regulates neurogenesis and neuronal migration via the Wnt signaling pathway.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by significantly reduced brain size.
- Mutations in the Abnormal Spindle Microcephaly (ASPM) gene are the most frequent cause of MCPH.
Purpose of the Study:
- To investigate the role of Aspm in brain development.
- To elucidate the molecular mechanisms by which ASPM influences neurogenesis and neuronal migration.
Main Methods:
- Utilized gene knockdown (siRNA) to assess Aspm function.
- Investigated the Wnt signaling pathway's interaction with ASPM.
- Employed stabilized β-catenin expression to rescue Aspm knockdown phenotypes.
Main Results:
- Aspm expression is crucial for proper neurogenesis and neuronal migration.
- ASPM acts as a positive regulator of Wnt signaling.
- Aspm knockdown leads to reduced Wnt-mediated transcription, which can be rescued by stabilized β-catenin.
Conclusions:
- Aspm plays a critical role in Wnt-mediated neurogenesis and neuronal migration programs.
- Dysregulation of Aspm's function in Wnt signaling may contribute to the etiology of certain psychiatric disorders.
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