Exogenous FGF-4 can suppress anterior development in the mouse embryo during neurulation and early organogenesis

Dev Biol. 2000 May 1;221(1):41-52. doi: 10.1006/dbio.2000.9663.

Abstract

Members of the fibroblast growth factor (FGF) family of peptide growth factors are widely expressed in the germ layer derivatives during gastrulation and early organogenesis of the mouse. We have investigated the effect of administering recombinant FGF-4 in the late-primitive streak stage embryo to test if the patterning of the body plan may be influenced by this growth factor. Shortly after FGF treatment the embryonic tissues up-regulated the expression of Brachyury and the RTK signaling regulator Spry2, suggesting that FGF signaling was activated as an immediate response to exogenous FGF. Concomitantly, Hesx1 expression was suppressed in the prospective anterior region of the embryo. After 24 h of in vitro development, embryos displayed a dosage-related suppression of forebrain morphogenesis, disruption of the midbrain-hindbrain partition, and inhibition of the differentiation of the embryonic mesoderm. Overall, development of the anterior-posterior axis in the late gastrula is sensitive to the delivery of exogenous FGF-4. The early response associated with the expression of Spry2 suggests that the later phenotype observed could be primarily related to an inhibition of the FGF signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Body Patterning / drug effects*
  • Brain / embryology*
  • Embryonic and Fetal Development / drug effects*
  • Fetal Proteins*
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects
  • Homeodomain Proteins / genetics
  • Humans
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Protein-Serine-Threonine Kinases
  • Proteins / genetics
  • Proto-Oncogene Proteins / pharmacology*
  • Recombinant Proteins / pharmacology
  • Repressor Proteins
  • Signal Transduction
  • T-Box Domain Proteins / genetics
  • Transcription Factor HES-1

Substances

  • Adaptor Proteins, Signal Transducing
  • Basic Helix-Loop-Helix Transcription Factors
  • FGF4 protein, human
  • Fetal Proteins
  • Fgf4 protein, mouse
  • Fibroblast Growth Factor 4
  • HESX1 protein, human
  • Hes1 protein, mouse
  • Hesx1 protein, mouse
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • SPRY2 protein, human
  • T-Box Domain Proteins
  • Transcription Factor HES-1
  • HES1 protein, human
  • Fibroblast Growth Factors
  • Protein-Serine-Threonine Kinases
  • Spry2 protein, mouse
  • Brachyury protein