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Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm.

Approximately 10% of cases of Alzheimer's disease are familial and associated with autosomal dominant inheritance of mutations in genes encoding the amyloid precursor protein, presenilin 1 (PS1) and presenilin 2 (PS2). Mutations in PS1 are linked to about 25% of cases of early-onset familial Alzheimer's disease. PS1, which is endoproteolytically processed in vivo, is a multipass transmembrane protein and is a functional homologue of SEL-12, a Caenorhabditis elegans protein that facilitates signalling mediated by the Notch/LIN-12 family of receptors. To examine potential roles for PS1 in facilitating Notch-mediated signalling during mammalian embryogenesis, we generated mice with targeted disruptions of PS1 alleles (PS1-/- mice). PS1-/- embryos exhibited abnormal patterning of the axial skeleton and spinal ganglia, phenotypes traced to defects in somite segmentation and differentiation. Moreover, expression of mRNA encoding Notch1 and Dll1 (delta-like gene 1), a vertebrate Notch ligand, is markedly reduced in the presomitic mesoderm of PS1-/- embryos compared to controls. Hence, PS1 is required for the spatiotemporal expression of Notch1 and Dll1, which are essential for somite segmentation and maintenance of somite borders.

Pubmed ID: 9153393


  • Wong PC
  • Zheng H
  • Chen H
  • Becher MW
  • Sirinathsinghji DJ
  • Trumbauer ME
  • Chen HY
  • Price DL
  • Van der Ploeg LH
  • Sisodia SS



Publication Data

May 15, 1997

Associated Grants


Mesh Terms

  • Animals
  • Body Patterning
  • Central Nervous System
  • Embryonic and Fetal Development
  • Gene Targeting
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mesoderm
  • Mice
  • Presenilin-1
  • Protein Precursors
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Transcription Factors