Analysis of mouse embryonic patterning and morphogenesis by forward genetics
Journal - PNAS
Many aspects of the genetic control of mammalian embryogenesiscannot be extrapolated from other animals. Taking a forwardgenetic approach, we have induced recessive mutations by treatmentof mice with ethylnitrosourea and have identified 43 mutationsthat affect early morphogenesis and patterning, including 38genes that have not been studied previously. The molecular lesionsresponsible for 14 mutations were identified, including mutationsin nine genes that had not been characterized previously. Somemutations affect vertebrate-specific components of conservedsignaling pathways; for example, at least five mutations affectpreviously uncharacterized regulators of the Sonic hedgehog(Shh) pathway. Approximately half of all of the mutations affectthe initial establishment of the body plan, and several of theseproduce phenotypes that have not been described previously.A large fraction of the genes identified affect cell migration,cellular organization, and cell structure. The findings indicatethat phenotype-based genetic screens provide a direct and unbiasedmethod to identify essential regulators of mammalian development.
This contribution is part of the special series of InauguralArticles by members of the National Academy of Sciences electedon April 20, 2004.
Abbreviations: ENU, ethylnitrosourea; SSLP, simple sequencelength polymorphism; en, embryonic day n; Smo, Smoothened; bnb,bent body; Hh, Hedgehog; IFT, intraflagellar transport; lzme,lazy mesoderm.
See accompanying Biography on page 5910. Present address: Department of Molecular Biology, PrincetonUniversity Lewis Thomas Laboratory, Washington Road, LTL110,Princeton, NJ 08546. Present address: Department of Human Genetics, Emory UniversitySchool of Medicine, Whitehead Research Building, 615 MichaelStreet, Suite 301, Atlanta, GA 30322.** Present address: Department of Cell and Developmental Biology,Weill Cornell Medical College, 1300 York Avenue, New York, NY10021.© 2005 by The National Academy of Sciences of the USA
|Keywords : ||ethylnitrosourea • hedgehog • intraflagellar transport • mesoderm • neural tube closure|