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Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation
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Rheb is essential for murine development.

Susanna M I Goorden1, Marianne Hoogeveen-Westerveld, Caroline Cheng

  • 1Department of Neuroscience, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.

Molecular and Cellular Biology
|February 16, 2011
PubMed
Summary

Ras homolog enriched in brain (Rheb) is crucial for mammalian development, as Rheb knockout embryos exhibited midgestation lethality. Genetic interaction between Tsc1 and Rheb was observed in mice.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Ras homolog enriched in brain (Rheb) is a key signaling intermediate linking growth factors to the mechanistic target of rapamycin complex 1 (TORC1) pathway.
  • TORC1 signaling regulates cell growth, proliferation, and metabolism.

Purpose of the Study:

  • To investigate the essential role of Rheb in mammalian development and TORC1 signaling.
  • To characterize the in vivo function of Rheb using a knockout mouse model.

Main Methods:

  • Generation of Rheb knockout (Rheb(-/-)) mice.
  • Analysis of embryonic development and viability.
  • Assessment of TORC1 activity in Rheb(-/-) embryonic fibroblasts.
  • Evaluation of genetic interactions with Tsc1 deficiency.

Main Results:

  • Rheb(-/-) embryos exhibited normal inner cell mass differentiation but died around midgestation, primarily due to cardiovascular defects.
  • Rheb(-/-) embryonic fibroblasts displayed reduced TORC1 activity, smaller cell size, and impaired proliferation.
  • Rheb heterozygosity prolonged the survival of Tsc1(-/-) embryos, indicating a genetic interaction.

Conclusions:

  • Rheb is essential for embryonic development in mammals, particularly for cardiovascular system formation.
  • Rheb plays a critical role in TORC1 pathway regulation, influencing cell size and proliferation.
  • A significant genetic interaction exists between Tsc1 and Rheb in mouse development.