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PMID:21937711

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Citation

Buchman, JJ, Durak, O and Tsai, LH (2011) ASPM regulates Wnt signaling pathway activity in the developing brain. Genes Dev. 25:1909-14

Abstract

Autosomal recessive primary microcephaly (MCPH) is a neural developmental disorder in which patients display significantly reduced brain size. Mutations in Abnormal Spindle Microcephaly (ASPM) are the most common cause of MCPH. Here, we investigate the underlying functions of Aspm in brain development and find that Aspm expression is critical for proper neurogenesis and neuronal migration. The Wnt signaling pathway is known for its roles in embryogenesis, and genome-wide siRNA screens indicate that ASPM is a positive regulator of Wnt signaling. We demonstrate that knockdown of Aspm results in decreased Wnt-mediated transcription, and that expression of stabilized β-catenin can rescue this deficit. Finally, coexpression of stabilized β-catenin can rescue defects observed upon in vivo knockdown of Aspm. Our findings provide an impetus to further explore Aspm's role in facilitating Wnt-mediated neurogenesis programs, which may contribute to psychiatric illness etiology when perturbed.

Links

PubMed PMC3185963 Online version:10.1101/gad.16830211

Keywords

Animals; Brain/embryology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Mice; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/cytology; Signal Transduction; Stem Cells/cytology; Wnt Proteins/metabolism; beta Catenin/genetics; beta Catenin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ASPM

acts_upstream_of_or_within

GO:0001764: neuron migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:17544)
  • results_in_movement_of:(CL:0000117)

Seeded From UniProt

complete

MOUSE:ASPM

acts_upstream_of_or_within

GO:0001764: neuron migration

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88276

P

  • occurs_in:(EMAPA:17544)
  • results_in_movement_of:(CL:0000117)

Seeded From UniProt

complete

MOUSE:ASPM

acts_upstream_of_or_within

GO:0002052: positive regulation of neuroblast proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ASPM

acts_upstream_of_or_within

GO:0002052: positive regulation of neuroblast proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88276

P

Seeded From UniProt

complete

MOUSE:ASPM

acts_upstream_of_or_within

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88276

P

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0001764: neuron migration

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1334448

P

  • occurs_in:(EMAPA:17544)
  • results_in_movement_of:(CL:0000117)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0002052: positive regulation of neuroblast proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1334448

P

Seeded From UniProt

complete


See also

References

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