Analysis of notch function in presomitic mesoderm suggests a γ-secretase-independent role for presenilins in somite differentiation

Stacey S. Huppert, Ma Xenia G. Ilagan, Bart De Strooper, Raphael Kopan

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

The role of Notch signaling in general and presenilin in particular was analyzed during mouse somitogenesis. We visualize cyclical production of activated Notch (NICD) and establish that somitogenesis requires less NICD than any other tissue in early mouse embryos. Indeed, 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-, Pen-2-, and APH-1a-deficient embryos have anterior somites without γ-secretase, presenilin may have a γ-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.

Original languageEnglish
Pages (from-to)677-688
Number of pages12
JournalDevelopmental cell
Volume8
Issue number5
DOIs
StatePublished - May 2005

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