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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
PubMed

Insights

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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