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

Alexander Ermakov, Jonathan L. Stevens, Elaine Whitehill, Joan E. Robson, Guido Pieles, Debra Brooker, Paraskevi Goggolidou, Nicola Powles-Glover, Terry Hacker, Stephen R. Young, Neil Dear, Elizabeth Hirst, Zuzanna Tymowska-Lalanne, James Briscoe, Shoumo Bhattacharya, Dominic P. Norris

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages581-594
Number of pages14
JournalDevelopmental Dynamics
Volume238
Issue number3
DOIs
Publication statusPublished - 1 Mar 2009

Keywords

  • Cilia
  • ENU
  • Left-right
  • Mouse
  • Pulmonary

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Ermakov, A., Stevens, J. L., Whitehill, E., Robson, J. E., Pieles, G., Brooker, D., ... Norris, D. P. (2009). Mouse mutagenesis identifies novel roles for left-right patterning genes in pulmonary, craniofacial, ocular, and limb development. Developmental Dynamics, 238(3), 581-594. https://doi.org/10.1002/dvdy.21874