1994 Fiscal Year Final Research Report Summary
Development of methods for specifically inhibit FGF signalling system in vivo
| Project/Area Number |
05558100
|
|---|
| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
神経・脳内生理学
|
|---|
| Research Institution | University of Tokyo |
|---|
Principal Investigator |
OKAMOTO Harumasa Univ.Tokyo, Fac.Med., Assoc.Prof., 医学部(医), 助教授 (40134283)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kunitaro Univ.Tokyo, Fac.Med., Professor, 医学部(医), 教授 (10010034)
KENGAKU Mineko Univ.Tokyo, Fac.Med., DC fellow of Japanese Society for the Promotion of Science, 医学部(医), 日本学術振興会特別研
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Keywords | FGF / FGF receptor / Dominant-negative mutation / Xenopus laevis / Tyrocine kinase |
|---|
| Research Abstract |
Recently, fibroblast growth factor (FGF) has been shown to play a crucial role in the development, differentiation and maintenance of neuronal cells in vitro.
However, we do not know yet whether FGF plays a similar crucial role in the nervons system in vivo. To address this issue, we may need methods to inhibit the action of FGF specifically and without toxic effects. Introduction of dominant-negative form of FGF receptor into cells of interest seems a promising method in this respect. We choose developing embryos of Xenopus laevis as a model system to examine the availability of the method, in whid FGF acts as a neural inducer.
It has been reported that two distinct types of FGF receptor named XFGFR-1 and XFGFR-2 are expressed in Xenopus embryo. In the present research, we have cloned three new FGF receptor cDNAs from Xenopus gastrula, which we designated XFGFR-3, XFGFR-4 and XFGFR-5 based on their homology to the human FGF receptors FGFR-3 and FGFR-4, respectively (XFGFR-5 is highly homologous, but distinct from XFGFR-4) . To identify the Xenopus FGFreceptor subtype (s) which is involved in neural induction, we have determined the spatio-temporal expression patterns of these FGF receptors by RT-PCR and RNase protection assay, and found that XFGFR-2,4 and 5 were expressed at the right time and right place for the neural induction during early development. We have made dominant-negative form of these cDNAs, in which cytoplasmic tyrosine kinase domain is deleted. Detailed studies using these dominant-negative moleculess are in progress.
|
