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

Philip Chun 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 journalArticle

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

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Presenilin-1
Mesoderm
Gene Expression
Somites
Alzheimer Disease
Embryonic Structures
Presenilin-2
Caenorhabditis elegans Proteins
Genes
Mutation
Amyloid beta-Protein Precursor
Spinal Ganglia
Skeleton
Embryonic Development
Vertebrates
Alleles
Maintenance
Ligands
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Wong, P. C., Zheng, H., Chen, H., Becher, M. W., Sirinathsinghji, D. J. S., Trumbauer, M. E., ... Sisodia, S. S. (1997). Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm. Nature, 387(6630), 288-292. https://doi.org/10.1038/387288a0

Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm. / Wong, Philip Chun; Zheng, Hui; Chen, Hua; Becher, Mark W.; Sirinathsinghji, Dalip J S; Trumbauer, Myrna E.; Chen, Howard Y.; Price, Donald L.; Van Der Ploeg, Lex H T; Sisodia, Sangram S.

In: Nature, Vol. 387, No. 6630, 15.05.1997, p. 288-292.

Research output: Contribution to journalArticle

Wong, PC, Zheng, H, Chen, H, Becher, MW, Sirinathsinghji, DJS, Trumbauer, ME, Chen, HY, Price, DL, Van Der Ploeg, LHT & Sisodia, SS 1997, 'Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm', Nature, vol. 387, no. 6630, pp. 288-292. https://doi.org/10.1038/387288a0
Wong PC, Zheng H, Chen H, Becher MW, Sirinathsinghji DJS, Trumbauer ME et al. Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm. Nature. 1997 May 15;387(6630):288-292. https://doi.org/10.1038/387288a0
Wong, Philip Chun ; Zheng, Hui ; Chen, Hua ; Becher, Mark W. ; Sirinathsinghji, Dalip J S ; Trumbauer, Myrna E. ; Chen, Howard Y. ; Price, Donald L. ; Van Der Ploeg, Lex H T ; Sisodia, Sangram S. / Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm. In: Nature. 1997 ; Vol. 387, No. 6630. pp. 288-292.
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