PUBLICATION

A chemical genetic screen in zebrafish for pathways interacting with cdx4 in primitive hematopoiesis

Authors
Paik, E.J., de Jong, J.L., Pugach, E., Opara, P., and Zon, L.I.
ID
ZDB-PUB-100427-17
Date
2010
Source
Zebrafish   7(1): 61-68 (Journal)
Registered Authors
de Jong, Jill, Opara, Praise, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning/drug effects
  • Drug Evaluation, Preclinical
  • Female
  • Gene Expression Regulation, Developmental/drug effects
  • Genetic Testing
  • Hematopoiesis/drug effects*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Male
  • Phenotype
  • Signal Transduction/drug effects*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
20415644 Full text @ Zebrafish
Abstract
cdx4, a caudal-related homeodomain-containing transcription factor, functions as a regulator of hox genes, thereby playing a critical role in anterior-posterior (A-P) patterning during embryogenesis. In zebrafish, homozygous deletion of the cdx4 gene results in a mutant phenotype known as kugelig, with aberrant A-P patterning and severe anemia characterized by decreased gata1 expression in the posterior lateral mesoderm. To identify pathways that interact with cdx4 during primitive hematopoiesis, we conducted a chemical genetic screen in the cdx4 mutant background for compounds that increase gata1 expression in cdx4 mutants. Among 2640 compounds that were tested, we discovered two compounds that rescued gata1 expression in the cdx4-mutant embryos. The strongest rescue was observed with bergapten, a psoralen compound found in bergamont oil. Another member of the psoralen family, 8-methoxypsoralen, was also found to rescue gata1 expression in cdx4-mutant embryos. The psoralen compounds also disrupted normal A-P patterning of embryos. These compounds modify the cdx4-mutant phenotype and will help elucidate signaling pathways that act downstream or parallel to the cdx4-hox pathway.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping