Regulatory analysis of the mouse Fgf3 gene: control of embryonic expression patterns and dependence upon sonic hedgehog (Shh) signalling.
Fgf3 displays a dynamic and complex expression pattern during mouse embryogenesis. To address the molecular mechanisms underlying Fgf3 expression, we used a transgenic approach to assay genomic regions from the mouse Fgf3 gene for regulatory activity. We identified an enhancer that mediates major components of embryonic expression, governing expression in the midbrain, hindbrain, surface ectoderm, dorsal roots and dorsal root ganglia (DRG), proximal sensory ganglia, and the developing central nervous system (CNS). Deletional analysis of the enhancer further delimited this regulatory activity to a 5.7-kb fragment. We have also revealed sonic hedgehog (Shh) -dependent and Shh-independent aspects of Fgf3 expression through breeding the Fgf3 reporter transgene into Shh mutants. In the absence of Shh signalling, Fgf3 reporter expression is lost in the ventral CNS, DRG, and superior cervical nerves, whereas activation of reporter expression in cranial ganglion cells is Shh independent. Moreover, detailed re-examination of the Shh phenotype revealed that Shh signalling is required for the correct development/maturation of the DRG.
Powles
Nicola
N
Mammalian Genetics Unit, Medical Research Council, Harwell, Oxon, United Kingdom.
Marshall
Heather
H
Economou
Androulla
A
Chiang
Chin
C
Murakami
Akira
A
Dickson
Clive
C
Krumlauf
Robb
R
Maconochie
Mark
M
D000818:Animals; D002490:Central Nervous System / Q000196:embryology; D004742:Enhancer Elements, Genetic; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000196:embryology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D053823:Hedgehog Proteins; D006579:Heterozygote; D006720:Homozygote; D017403:In Situ Hybridization; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes
D051518:Fibroblast Growth Factor 3; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D005346:Fibroblast Growth Factors