Disease relevance of FGFR1

• To investigate the effects of inactivation of FGFR on the growth of malignant gliomas, we constructed a replication-deficient recombinant adenovirus vector encoding a truncated form of chicken FGFR1 (AxCA delta FR) [1].
• METHODS: Lenses were injected on embryonic day (E)3 with replication-defective retroviruses that express full-length or truncated FGF receptor (FGFR)-1 or a secreted form of FGF1 [2].

High impact information on FGFR1

• Patterns of expression of transcripts encoding receptors for fibroblast growth factor and nerve growth factor (FGF-R and NGF-R) in the developing chick nervous system are compared using in situ hybridization histochemistry [3].
• The pattern of NGF-R expression is generally reciprocal to that of FGF-R in the CNS and in some phases of development of the PNS [3].
• These experiments provide in vivo evidence to support the hypothesis that regulation of FGF receptor levels may function as a mechanism for controlling FGF-dependent processes during embryonic development [4].
• Because endogenous chick FGF may remain bound to FGF receptor in membrane preparations, membranes were treated with acidic (pH 4.0) buffers to release bound FGF; such treatment did not affect 125I-aFGF binding and moderately increased the number of binding sites in day-7 and -19 embryos [4].
• Consequently, the observed loss of high affinity 125I-aFGF binding sites and FGF-binding polypeptides most likely represents a loss of FGF receptor protein [4].

Biological context of FGFR1

• Differential expression of these FGF receptor genes suggested that differential roles of these receptors in epithelia-mesenchymal interactions of limb and feather morphogenesis [5].
• Retina regeneration in the chick embryo is not induced by spontaneous Mitf downregulation but requires FGF/FGFR/MEK/Erk dependent upregulation of Pax6 [6].
• We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles [7].
• These studies demonstrate that the FGFR1 promoter is activated by Sp transcription factors in proliferating myoblasts and demonstrate at least part of the mechanism by which FGFR1 gene expression is down-regulated in differentiated muscle fibers [8].
• RESULTS: Lens fiber cell differentiation was not inhibited in cells infected with virus expressing truncated FGFR1 [2].

Anatomical context of FGFR1

• Here we show the expression patterns of three FGF receptors, (FGFR1, FGFR2 and FGFR3) in embryonic stages between gastrulation and limb bud formation, focussing particularly on neural tissues [9].
• During early neuromere formation FGFR1 transcripts are present throughout the neural tube, while transcripts for FGFR2 and FGFR3 become restricted to regions of the diencephalon and spinal cord [9].
• During later neuromere development, FGFR1 transcripts become localised to the telencephalon, anterior dorsal diencephalon and throughout the midbrain and hindbrain, whereas FGFR2 mRNA is restricted to dorsal telencephalon, dorsoanterior midbrain and hindbrain [9].
• Expression of FGFR1 was observed in the mesoderm of limb bud, in the mesenchyme just underneath the feather placode, and then in the anterior mesenchyme of the feather bud [5].
• The expression patterns of two distinct types of fibroblast growth factor receptor (FGFR) genes, FGFR1 and FGFR2, were compared during early chick eye development [10].

Associations of FGFR1 with chemical compounds

• In a previous study, we demonstrated that FGFR1 activity within the organizer is required for the production of both the somitic muscle- and pronephros-patterning signals by the organizer and the expression of chordin, an organizer-specific secreted protein (Mitchell and Sheets [2001] Dev. Biol. 237:295-305) [11].
• Its amino acid sequence suggests that the Cek1 protein is a transmembrane tyrosine kinase and presumably the receptor for an unknown ligand [12].
• The observed correlation between the level of FREK gene expression and various stages of differentiation, its modulation by b-FGF and RA, as well as the correlation between FREK gene expression and the physiological response to b-FGF, suggest that this specific FGF receptor plays an important role in muscle and cartilage cell differentiation [13].
• This data suggests that retinoic acid may be affecting other aspects of the FGF receptor-ligand interaction [14].

Regulatory relationships of FGFR1

• Ectopic Mitf expression was able to inhibit transdifferentiation by acting downstream of FGFR/MEK/Erk signaling, likely by inhibiting the increase in Pax6 protein in the RPE [6].

Other interactions of FGFR1

• CONCLUSIONS: FGF2 stimulates Pax6 expression during induction of transdifferentiation of the RPE through FGFR/MEK/Erk signaling cascade [6].
• After this stage, the level of expression of FGF-R1 increases and its peak of expression at embryonic day 18 is concomitant with the detection of the opsin transcript [15].
• FGF10 and FGF receptor inhibition cause opposed effects on cell determination and cell proliferation [16].
• Furthermore, we cloned a novel FGF receptor-like molecule as well as two novel putative RTKs related to the vascular endothelial growth factor (VEGF) receptor [17].
• Fgf19 expression initiated in the forebrain, and then became restricted to the distal portion of the optic vesicle abutting the future lens placode, where FGF receptor 4 (Fgfr4), a receptor for FGF19, was expressed [18].

Analytical, diagnostic and therapeutic context of FGFR1

• Site directed mutagenesis and transfection studies indicated that both Sp1 sites are functional and both are required for FGFR1 promoter activity [19].
• Antibodies prepared to the cloned Cek1 kinase recognize, in immunoblotting experiments, two protein bands with apparent molecular weights of 100,000 and 110,000 [12].
• Here we report the molecular cloning and sequence of a new member of the FGF receptor family, denoted flg-2, which was isolated from a human keratinocyte cDNA library [20].
• Northern blot analysis of RNA of the whole retina was used to observe that FGF-R1 transcripts are abundant at embryonic day 4 and then decrease until day 11 [15].
• Immunohistochemistry for CEK1 showed that normal hair cells expressed the receptor heavily on the hair cell stereocilia, while with early damage, CEK1 came to be expressed heavily on the apical surfaces of the supporting cells [21].

References