PUBLICATION

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation

Authors
Yan, Y.T., Gritsman, K., Ding, J., Burdine, R.D., Corrales, J.D., Price, S.M., Talbot, W.S., Schier, A.F., and Shen, M.M.
ID
ZDB-PUB-991102-22
Date
1999
Source
Genes & Development   13(19): 2527-2537 (Journal)
Registered Authors
Burdine, Rebecca, Gritsman, Kira, Schier, Alexander, Talbot, William S., Yan, Yi-Lin
Keywords
none
MeSH Terms
  • Animals
  • Axis, Cervical Vertebra
  • Body Patterning*
  • Embryonic and Fetal Development
  • Epidermal Growth Factor/genetics
  • Epidermal Growth Factor/metabolism*
  • Gene Expression
  • Gene Targeting
  • Growth Substances/genetics
  • Growth Substances/metabolism*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Intercellular Signaling Peptides and Proteins*
  • Mice
  • Mutagenesis
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish
  • Zebrafish Proteins*
PubMed
10521397 Full text @ Genes & Dev.
Abstract
Specification of the left-right (L-R) axis in the vertebrate embryo requires transfer of positional information from the node to the periphery, resulting in asymmetric gene expression in the lateral plate mesoderm. We show that this activation of L-R lateral asymmetry requires the evolutionarily conserved activity of members of the EGF-CFC family of extracellular factors. Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Similarly, zebrafish one-eyed pinhead (oep) mutants that have been rescued partially by mRNA injection display heterotaxia, including randomization of heart looping and pancreas location. In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the prospective floor plate. Notably, L-R asymmetric expression of Nodal at the lateral edges of the node is still observed in Cryptic mutants, indicating that L-R specification has occurred in the node but not the lateral plate. Combined with the previous finding that oep is required for nodal signaling in zebrafish, we propose that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping