Abstract
The present study elucidates the molecular structure of a murine fibroblast growth factor 1 (FGF-1) promoter and describes its distribution in the adult and developing mouse brain. A cDNA clone coding for FGF-1 was isolated from a mouse brain cDNA library. Nucleotide sequence analysis revealed that the clone contained, in addition to the protein coding region, an untranslated exon (FGF-1B) 34 base pairs upstream of the translation start codon ATG. The mouse cDNA clone corresponded to the sole FGF-1 transcript in the brain. An RNase protection assay was used to map the transcription start site of the 1B promoter. The sequences upstream from the major transcription initiation site lacked consensus TATA or CAAT boxes. In situ hybridization with cRNA probes specific for the 1B transcript showed the message to be restricted largely to sensory and motor nuclei in the brainstem, and to the ventral spinal cord and cerebellum. Although occasional brainstem nuclei were labeled at low levels by embryonic day 18, the majority of nuclei became detectable autoradiographically during postnatal weeks 1 and 2, and adult levels of grain density were reached during the 3rd and 4th postnatal weeks. FGF-1B mRNA was expressed in phylogenetically older brain regions, which are involved primarily in processing information from exteroceptive sensory mechanoreceptors and in motor control. The relatively late developmental expression suggests a role for FGF-1 in neuronal maturation, rather than in neurogenesis.
Highlights
Acidic fibroblast growth factor, known as fibroblast growth factor 1 (FGF-1),1 is one of the nine members of the FGF family [1,2,3]
The complete nucleotide sequence of the FGF-1 cDNA was determined by the chain termination method (Fig. 1B)
We report here the isolation of a full-length murine brain FGF-1 cDNA containing a 5Ј-untranslated exon -1B spliced to the first protein-coding exon
Summary
Known as fibroblast growth factor 1 (FGF-1), is one of the nine members of the FGF family [1,2,3] All proteins in this family have 30 –50% amino acid sequence similarity and a similar exon/intron structure in the protein coding region of the gene [4, 5]. Within the central nervous system, FGF-1 has been shown to stimulate glial mitogenesis [13, 14] and to have trophic effects [15]. Within the human brain [23] and retina [27], the FGF-1B transcript predominates Both FGF-1 mRNA and its protein have been anatomically localized within the central nervous system of adult rodents (28 –32). The FGF-1B promoter that is active in the murine brain was isolated, its structure was defined, and its distribution in the adult and developing mouse brain was determined
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