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Notch1 is essential for postimplantation development in mice

P J Swiatek1, C E Lindsell, F F del Amo

  • 1Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.

Genes & Development
|March 15, 1994
PubMed
Summary

The mouse Notch1 gene is essential for embryonic development. Homozygous Notch1 mutant embryos exhibit widespread cell death and die before 11.5 days of gestation, indicating a vital role in early development.

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • The Notch gene family encodes transmembrane proteins crucial for cell fate determination.
  • Notch homologs are evolutionarily conserved across species, including vertebrates.
  • Notch1 is a key mouse homolog involved in developmental processes.

Purpose of the Study:

  • To investigate the in vivo function of the mouse Notch1 gene.
  • To characterize the developmental consequences of Notch1 loss-of-function mutations.

Main Methods:

  • Targeted gene disruption in embryonic stem cells to create Notch1 mutant mice.
  • Intercrosses of heterozygous mice to obtain homozygous mutants.
  • Morphological and histological analyses of mutant embryos at various gestational stages.

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Main Results:

  • No live-born homozygous Notch1 mutant offspring were observed.
  • Homozygous mutant embryos died before embryonic day 11.5.
  • Post-gestational day 9, mutant embryos showed widespread cell death, not linked to placental or vascular defects.
  • Notch2 expression partially overlapped with Notch1 expression.
  • The Notch1 mutation was not allelic to the Danforth's short tail (Sd) mutation.

Conclusions:

  • The Notch1 gene is indispensable for early postimplantation development in mice.
  • Notch1 plays a critical role in preventing cell death during embryonic development.
  • Further research into Notch signaling pathways in mammalian development is warranted.