Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm
| Autor: | Philip C. Wong, Myrna E. Trumbauer, Dalip J. S. Sirinathsinghji, Donald L. Price, Lex H.T. Van der Ploeg, Hua Chen, Mark W. Becher, Howard Y. Chen, Sangram S. Sisodia, Hui Zheng |
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| Rok vydání: | 1997 |
| Předmět: |
Central Nervous System
Mesoderm animal diseases Receptors Cell Surface Biology Presenilin Embryonic and Fetal Development Mice PEN-2 mental disorders Presenilin-1 medicine Paraxial mesoderm Animals Protein Precursors Receptor Notch1 APH-1 Notch 1 Body Patterning Genetics Multidisciplinary Intracellular Signaling Peptides and Proteins Membrane Proteins nervous system diseases Gamma-secretase complex Cell biology Somite medicine.anatomical_structure nervous system Gene Targeting biology.protein Transcription Factors |
| Zdroj: | Nature. 387:288-292 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Approximately 10% of cases of Alzheimer's disease are familial and associated with autosomal dominant inheritance of mutations in genes encoding the amyloid precursor protein1, presenilin 1 (PS1)2 and presenilin 2 (PS2)3,4. Mutations in PS1 are linked to about 25% of cases of early-onset familial Alzheimer's disease5. PS1, which is endoproteolytically processed in vivo6, is a multipass transmembrane protein and is a functional homologue of SEL-12 (ref. 7), a Caenorhabditis elegans protein that facilitates signalling mediated by the Notch/LIN-12 family of receptors8,9. 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 DII 1 (delta-like gene I)10, 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 Dll 1, which are essential for somite segmentation and maintenance of somite borders11–13. |
| Databáze: | OpenAIRE |
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