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Intramembrane Proteolysis Independent Function Of Presenilin Links Notch And Wnt Signaling In The Somite
Author(s) -
Huppert Stacey S.,
Chandu Dilip,
Ilagan Maxene,
Kopan Raphael
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a423-b
Subject(s) - somitogenesis , presenilin , notch signaling pathway , somite , biology , microbiology and biotechnology , notch proteins , hes3 signaling axis , embryo , anatomy , signal transduction , genetics , medicine , embryogenesis , alzheimer's disease , disease
The role of Notch signaling in general and presenilin in particular was analyzed during mouse somitogenesis. We establish that a Val to Gly mutaion in the Notch TMD reduced proteolysis. Somitogenesis requires less NICD than any other tissue in early mouse embryos‐ formation of cervical somites proceeds in Notch1; Notch2 deficient embryos. This is in contrast to mice lacking all presenilin alleles, which have no somites. Since Nicastrin‐deficient embryos have anterior somites without g‐secretase, presenilin may have a g‐secretase‐independent role in somitogenesis. Embryos triple homozygous for both presenilin null alleles and a Notch allele that is a poor substrate for presenilin (N1V‐>G), experience fortuitous cleavage of N1V‐>G by another protease. This restores NICD, anterior segmentation, and bilateral symmetry, but does not rescue rostral/caudal identities. These data clarify multiple roles for Notch signaling during segmentation, and suggest that the earliest stages of somitogenesis are regulated by both Notch‐dependent and Notch‐independent functions of presenilin.