Mouse mutagenesis identifies novel roles for left-right patterning genes in pulmonary, craniofacial, ocular, and limb development

Dev Dyn. 2009 Mar;238(3):581-94. doi: 10.1002/dvdy.21874.


Vertebrate organs show consistent left-right (L-R) asymmetry in placement and patterning. To identify genes involved in this process we performed an ENU-based genetic screen. Of 135 lines analyzed 11 showed clear single gene defects affecting L-R patterning, including 3 new alleles of known L-R genes and mutants in novel L-R loci. We identified six lines (termed "gasping") that, in addition to abnormal L-R patterning and associated cardiovascular defects, had complex phenotypes including pulmonary agenesis, exencephaly, polydactyly, ocular and craniofacial malformations. These complex abnormalities are present in certain human disease syndromes (e.g., HYLS, SRPS, VACTERL). Gasping embryos also show defects in ciliogenesis, suggesting a role for cilia in these human congenital malformation syndromes. Our results indicate that genes controlling ciliogenesis and left-right asymmetry have, in addition to their known roles in cardiac patterning, major and unexpected roles in pulmonary, craniofacial, ocular and limb development with implications for human congenital malformation syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning / genetics*
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Extremities / embryology*
  • Eye / embryology*
  • Eye / metabolism
  • Facial Bones / embryology*
  • Facial Bones / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Mice
  • Microscopy, Electron, Scanning
  • Molecular Sequence Data
  • Mutagenesis / genetics*
  • Mutation / genetics
  • Phenotype
  • Respiratory System / embryology*
  • Respiratory System / metabolism
  • Sequence Alignment