Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm

Philip C. Wong, Hui Zheng, Hua Chen, Mark W. Becher, Dalip J.S. Sirinathsinghji, Myrna E. Trumbauer, Howard Y. Chen, Donald L. Price, Lex H.T. Van Der Ploeg, Sangram S. Sisodia

Research output: Contribution to journalArticlepeer-review

Abstract

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 Notch 1 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 Notch 1 and Dll1, which are essential for somite segmentation and maintenance of somite borders.

Original languageEnglish (US)
Pages (from-to)288-292
Number of pages5
JournalNature
Volume387
Issue number6630
DOIs
StatePublished - May 15 1997

ASJC Scopus subject areas

  • General

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