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Mouse mutagenesis identifies novel roles for left–right patterning genes in pulmonary, craniofacial, ocular, and limb development
Author(s) -
Ermakov Alexander,
Stevens Jonathan L.,
Whitehill Elaine,
Robson Joan E.,
Pieles Guido,
Brooker Debra,
Goggolidou Paraskevi,
PowlesGlover Nicola,
Hacker Terry,
Young Stephen R.,
Dear Neil,
Hirst Elizabeth,
TymowskaLalanne Zuzanna,
Briscoe James,
Bhattacharya Shoumo,
Norris Dominic P.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21874
Subject(s) - biology , ciliogenesis , craniofacial , exencephaly , cilium , phenotype , genetics , polydactyly , limb development , craniofacial abnormality , gene , anatomy , fetus , teratology , pregnancy
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. Developmental Dynamics 238:581–594, 2009. © 2009 Wiley‐Liss, Inc.