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Related Experiment Videos

Analysis of mouse embryonic patterning and morphogenesis by forward genetics.

María J García-García1, Jonathan T Eggenschwiler, Tamara Caspary

  • 1Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 10, 2005
PubMed
Summary

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Forward genetic screens in mice identified 43 mutations impacting early mammalian development and body plan formation. This research uncovers novel genes essential for embryogenesis, including regulators of the Sonic hedgehog pathway.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Mammalian embryogenesis has unique genetic controls distinct from other animals.
  • Understanding early development requires identifying key regulatory genes.

Purpose of the Study:

  • To identify novel genes controlling mammalian embryogenesis using a forward genetic screen.
  • To characterize mutations affecting early morphogenesis and body plan establishment.

Main Methods:

  • Induced recessive mutations in mice using ethylnitrosourea (ENU).
  • Phenotypic analysis of resulting mutations affecting embryonic development.
  • Molecular identification of gene lesions for characterized mutations.

Main Results:

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  • Identified 43 mutations affecting early morphogenesis and patterning.
  • Discovered 38 previously unstudied genes and characterized 9 new genes.
  • Found mutations in regulators of conserved signaling pathways, including the Sonic hedgehog (Shh) pathway.
  • Observed phenotypes related to body plan establishment, cell migration, organization, and structure.

Conclusions:

  • Phenotype-based genetic screens are effective for unbiased identification of essential mammalian developmental regulators.
  • New genes and pathways critical for vertebrate-specific developmental processes have been uncovered.