Canonical Notch signaling is dispensable for early cell fate specifications in mammals.

The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoderm, or ectoderm germ layers. Transcripts of Notch signaling pathway genes are present during mouse blastogenesis, suggesting that the canonical Notch signaling pathway may also function in early mammalian development. To test this directly, we used conditional deletion in oocytes carrying a ZP3Cre recombinase transgene to generate mouse embryos lacking both maternal and zygotic protein O-fucosyltransferase 1, a cell-autonomous and essential component of canonical Notch receptor signaling. Homozygous mutant embryos derived from eggs lacking Pofut1 gene transcripts developed indistinguishably from the wild type until approximately embryonic day 8.0, a postgastrulation stage after the formation of the three germ layers. Thus, in contrast to the case with C. elegans and sea urchins, canonical Notch signaling is not required in mammals for earliest cell fate specifications or for formation of the three germ layers. The use of canonical Notch signaling for early cell fate specifications by lower organisms may represent co-option of a regulatory pathway originally used later in development by all metazoa.