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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.

Original publication

DOI

10.1002/dvdy.21874

Type

Journal article

Journal

Dev Dyn

Publication Date

03/2009

Volume

238

Pages

581 - 594

Keywords

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