TY - JOUR
T1 - Mouse mutagenesis identifies novel roles for left-right patterning genes in pulmonary, craniofacial, ocular, and limb development
AU - Ermakov, Alexander
AU - Stevens, Jonathan L.
AU - Whitehill, Elaine
AU - Robson, Joan E.
AU - Pieles, Guido
AU - Brooker, Debra
AU - Goggolidou, Paraskevi
AU - Powles-Glover, Nicola
AU - Hacker, Terry
AU - Young, Stephen R.
AU - Dear, Neil
AU - Hirst, Elizabeth
AU - Tymowska-Lalanne, Zuzanna
AU - Briscoe, James
AU - Bhattacharya, Shoumo
AU - Norris, Dominic P.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - Cilia
KW - ENU
KW - Left-right
KW - Mouse
KW - Pulmonary
UR - http://www.scopus.com/inward/record.url?scp=61649114214&partnerID=8YFLogxK
U2 - 10.1002/dvdy.21874
DO - 10.1002/dvdy.21874
M3 - Article
C2 - 19235720
AN - SCOPUS:61649114214
SN - 1058-8388
VL - 238
SP - 581
EP - 594
JO - Developmental Dynamics
JF - Developmental Dynamics
IS - 3
ER -