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Updated: Jul 31, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis
L Wojnowski1, L F Stancato, A C Larner
1Laboratory on Genetics, National Institute of Mental Health, Bethesda, MD, USA. lwojnowski@epidauros.com
Abstract:
The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from cell surface receptors to the nucleus. In vertebrates, Raf signaling has been implicated in the progression of mouse embryos through the two-cell stage and in the induction of posterior mesoderm. However, mouse embryos mutant for each of the Raf genes exhibit no developmental defects before mid-gestation. Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles. Our results show that Raf signaling is indeed indispensable for normal development beyond the blastocyst stage. However, due to a significant redundancy between Craf-1 and Braf, either gene is sufficient for normal development until mid-gestation. The molecular and developmental mechanisms for this redundancy were investigated by monitoring the expression of Raf genes throughout embryogenesis and by biochemical studies in mutant cell lines.
Insights
Raf signaling is essential for mouse embryonic development beyond the blastocyst stage. However, Craf-1 and Braf exhibit functional redundancy, allowing either gene to support development until mid-gestation.
Area of Science:
- Cellular signaling pathways
- Developmental biology
- Molecular genetics
Background:
- Mammalian Raf serine/threonine protein kinases (Raf) are key signal transducers.
- Raf signaling is linked to embryonic development in vertebrates.
- Previous studies showed no pre-mid-gestation defects in single Raf gene knockout mouse embryos.
Purpose of the Study:
- Investigate the role of Raf signaling in early mouse embryonic development.
- Determine the developmental consequences of combined Craf-1 and Braf mutations.
- Elucidate the mechanisms of functional redundancy between Craf-1 and Braf.
Main Methods:
- Generation and analysis of mouse mutants with combined Craf-1 and Braf alleles.
- Monitoring Raf gene expression during embryogenesis.
- Biochemical studies using mutant cell lines.
Main Results:
- Raf signaling is indispensable for development post-blastocyst stage.
- Significant functional redundancy exists between Craf-1 and Braf.
- Either Craf-1 or Braf alone supports normal development until mid-gestation.
Conclusions:
- Raf signaling plays a critical, albeit redundant, role in early mammalian development.
- Understanding Raf redundancy is key to deciphering developmental signaling pathways.
- Further research into molecular mechanisms underlying this redundancy is warranted.
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