Analysis of mouse embryonic patterning and morphogenesis by forward genetics.
Many aspects of the genetic control of mammalian embryogenesis cannot be extrapolated from other animals. Taking a forward genetic approach, we have induced recessive mutations by treatment of mice with ethylnitrosourea and have identified 43 mutations that affect early morphogenesis and patterning, including 38 genes that have not been studied previously. The molecular lesions responsible for 14 mutations were identified, including mutations in nine genes that had not been characterized previously. Some mutations affect vertebrate-specific components of conserved signaling pathways; for example, at least five mutations affect previously uncharacterized regulators of the Sonic hedgehog (Shh) pathway. Approximately half of all of the mutations affect the initial establishment of the body plan, and several of these produce phenotypes that have not been described previously. A large fraction of the genes identified affect cell migration, cellular organization, and cell structure. The findings indicate that phenotype-based genetic screens provide a direct and unbiased method to identify essential regulators of mammalian development.
García-García
María J
MJ
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Eggenschwiler
Jonathan T
JT
Caspary
Tamara
T
Alcorn
Heather L
HL
Wyler
Michael R
MR
Huangfu
Danwei
D
Rakeman
Andrew S
AS
Lee
Jeffrey D
JD
Feinberg
Evan H
EH
Timmer
John R
JR
Anderson
Kathryn V
KV
D000818:Animals; D019521:Body Patterning; D002874:Chromosome Mapping; D005808:Genes, Recessive; D008322:Mammals; D051379:Mice / Q000196:embryology* / Q000235:genetics*; D009024:Morphogenesis; D009154:Mutation; D009420:Nervous System / Q000196:embryology; D013045:Species Specificity