Ectopic expression of Fgf-4 in chimeric mouse embryos induces the expression of early markers of limb development in the lateral ridge.
The biological consequences of constitutive fibroblast growth factor-4 (fgf-4) expression were investigated in chimeric embryos prepared between wild-type host embryos and murine ES cells transfected with a construct in which expression of the murine fgf-4 gene was directed by the phosphoglycerate kinase (PGK-1) promoter. The embryos exhibit abnormalities of the limbs and the anterior central nervous system (CNS). The limb phenotype comprised the induction of outgrowth along the lateral ridge between the definitive fore and hind limbs resembling the early phases of limb development. The CNS defects comprised a complete absence, or marked reduction in forebrain and midbrain structures and rudimentary or absent eye development. Constitutive expression of fgf-4 was also accompanied by ectopic expression of the sonic hedgehog (shh) and msx-1 genes in the lateral ridge. These findings indicate that FGF exhibits multiple activities in early development which include the ability to induce the expression of early markers of limb development in the lateral ridge.
Abud
H E
HE
Department of Biochemistry, University of Oxford, Edgbaston, United Kingdom.
Skinner
J A
JA
McDonald
F J
FJ
Bedford
M T
MT
Lonai
P
P
Heath
J K
JK
D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D002490:Central Nervous System / Q000002:abnormalities; D002678:Chimera; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000648:ultrastructure; D005260:Female; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000096:biosynthesis; D017403:In Situ Hybridization; D018878:Limb Buds / Q000196:embryology* / Q000648:ultrastructure; D017880:Limb Deformities, Congenital; D051957:MSX1 Transcription Factor; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010735:Phosphoglycerate Kinase / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D013234:Stem Cells; D014157:Transcription Factors; D014162:Transfection
D017931:DNA Primers; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D005819:Genetic Markers; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D005346:Fibroblast Growth Factors; D010735:Phosphoglycerate Kinase