Expression and regulation of Sef, a novel signaling inhibitor of receptor tyrosine kinases-mediated signaling in the nervous system.
Fibroblast growth factors (FGFs) signal via four distinct high affinity cell surface tyrosine kinase receptors, termed FGFR1-FGFR4 (FGFR-FGF-receptor). Recently, a new modulator of the FGF signaling pathway, the transmembrane protein 'similar expression to FGF genes' (Sef), has been identified in zebrafish and subsequently in mammals. Sef from mouse and human inhibits FGF mitogenic activity. In the present study, we analyzed the expression of Sef in distinct rat brain areas, in the spinal cord and in peripheral nerves and spinal ganglia using semi-quantitative RT-PCR. Furthermore, we studied the cellular expression pattern of Sef in intact spinal ganglia and sciatic nerves and, in addition, after crush lesion, using in situ hybridization and immunohistochemistry. Sef transcripts were expressed in all brain areas evaluated and in the spinal cord. A neuronal expression was found in both intact and injured spinal ganglia. Intact sciatic nerves, however, showed little or no Sef expression. Seven days after injury, high Sef expression was concentrated to the crush site, and Schwann cells seemed to be the source of Sef. The labeling pattern of up-regulated Sef was complementary to the patterns of FGF-2 and FGFR1-3, which were localized proximal and distal to the crush site. These results suggest an involvement of Sef during the nerve regeneration process, possibly by fine-tuning the effects of FGF signaling.
Grothe
Claudia
C
Department of Neuroanatomy, OE 4140, Hannover Medical School, D-30623 Hannover, Germany. Grothe.Claudia@mh-hannover.de
Claus
Peter
P
Haastert
Kirsten
K
Lutwak
Ela
E
Ron
Dina
D
D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000293:injuries / Q000378:metabolism; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009409:Nerve Crush; D009420:Nervous System / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation
C518320:Il17rd protein, rat; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases