PUBLICATION
Lefty antagonism of squint is essential for normal gastrulation
- Authors
- Feldman, B., Concha, M.L., Saude, L., Parsons, M.J., Adams, R.J., Wilson, S.W., and Stemple, D.L.
- ID
- ZDB-PUB-030115-24
- Date
- 2002
- Source
- Current biology : CB 12(24): 2129-2135 (Journal)
- Registered Authors
- Adams, Richard, Concha, Miguel, Feldman, Benjamin, Parsons, Michael, Saude, Leonor, Stemple, Derek L., Wilson, Steve
- Keywords
- none
- MeSH Terms
-
- Mutation
- Signal Transduction
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Nodal Signaling Ligands
- Gene Deletion
- Body Patterning/genetics
- Endoderm/metabolism
- Left-Right Determination Factors
- Ectoderm/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Biomarkers
- Gastrula/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Animals
- Gene Expression Regulation, Developmental
- Transcription, Genetic
- Intracellular Signaling Peptides and Proteins
- Antisense Elements (Genetics)/pharmacology
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/metabolism*
- PubMed
- 12498688 Full text @ Curr. Biol.
Citation
Feldman, B., Concha, M.L., Saude, L., Parsons, M.J., Adams, R.J., Wilson, S.W., and Stemple, D.L. (2002) Lefty antagonism of squint is essential for normal gastrulation. Current biology : CB. 12(24):2129-2135.
Abstract
Activities of a variety of signaling proteins that regulate embryogenesis are limited by endogenous antagonists. The zebrafish Nodal-related ligands, Squint and Cyclops, and their antagonists, Lefty1 and Lefty2, belong to the TGFbeta-related protein superfamily, whose members have widespread biological activities. Among other activities, Nodals direct the formation of most mesendoderm. By inducing their own transcription and that of the Lefties, Nodal signals establish positive and negative autoregulatory loops. To investigate how these autoregulatory pathways regulate development, we depleted zebrafish embryos of Lefty1 and/or Lefty2 by using antisense morpholino oligonucleotides. Loss of Lefty1 causes aberrations during somitogenesis stages, including left-right patterning defects, whereas Lefty2 depletion has no obvious consequences. Depletion of both Lefty1 and Lefty2, by contrast, causes unchecked Nodal signaling, expansion of mesendoderm, and loss of ectoderm. The expansion of mesendoderm correlates with an extended period of rapid cellular internalization and a failure of deep-cell epiboly. The gastrulation defects of embryos depleted of Lefty1 and Lefty2 result from the deregulation of Squint signaling. In contrast, deregulation of Cyclops does not affect morphology or the transcription of Nodal target genes during gastrulation. Furthermore, we find that Cyclops is specifically required for the maintenance of lefty1 and lefty2 transcription.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping