Notch1 is essential for postimplantation development in mice.

Abstract

The Notch gene of Drosopbila encodes a large transmembrane protein involved in cell fate determination during embryonic and larval development. This gene is evolutionarily conserved, and Notch homologs have been cloned from several vertebrate species. To examine the in vivo role of the Notchl gene, a mouse homolog of Notch, a mutation was introduced by targeted disruption in embryonic stem cells, and these cells were used to generate mutant mice. Intercrosses of animals heterozygous for the Notchl mutation yielded no live-born homozygous mutant offspring. Homozygous mutant embryos died before 11.5 days of gestation. Morphological and histological analysis of the homozygous mutant embryos indicated that pattern formation through the first nine days of gestation appeared largely normal. However, histological analysis of mutant embryos subsequent to this stage revealed widespread cell death. Death of mutant embryos did not appear to be attributable to defects in placentation or vascularization. Examination of the RNA expression pattern of the Notch2 gene, another Notch gene family member, indicated that it partially overlapped the Notchl expression pattern. Genetic analysis of the Notchl mutation also demonstrated that it was not allelic to a mouse mutation described previously, Danforth's short tail (Sd). These results demonstrate that the Notchl gene plays a vital role during early postimplantation development in mice.

Morphological Variation of “Complex Vertebral Malformation” in Holstein Calves

“…5,9,10,13,22 Extensive fetal mortality has been reported in Notch1-or Notch2-deficient murine embryos, 5,9,22 whereas Fringe-deficient fetuses survived until birth. However, although severely affected neonates died, less affected mice could survive until adulthood.…”

Neoplastic transformation by Notch is independent of transcriptional activation by RBP-J signalling

“…The phenotype of mutant mice lacking either RBP-J or Notch1 is almost identical, indicating that RBP-J might be the major downstream target of Notch signalling in development (Swiatek et al, 1994;Conlon et al, 1995;Oka et al, 1995;de la Pompa et al, 1997). RBP-J represses transcription by binding to speci®c sequence motifs in the promoter of genes and recruits corepressors like SMRT or CIR (Dou et al, 1994;Kao et al, 1998;Hsieh et al, 1999).…”

Transit-Amplifying Ductular (Oval) Cells and Their Hepatocytic Progeny Are Characterized by a Novel and Distinctive Expression of Delta-Like Protein/Preadipocyte Factor 1/Fetal Antigen 1

“…Identified initially in invertebrates, four members of the Delta family, Delta1, Delta2, Delta3, and Delta4, 18 -20 and two of the Jagged/Serrate family (Serrate is the Drosophila homologue), Jagged1 and Jagged2, 21,22 have been characterized in mammals thus far. Notch function has been studied extensively in mouse models, in which it is involved in early pattern formation of the embryo, 23,24 as well as stem cell fate specification in brain, skin, pancreas, and hemopoietic tissue. [25][26][27][28][29] Delta-like protein (dlk) also belongs to the EGF-like homeotic protein family.…”