FGFR IN MIDBRAIN · Role of fgf receptor 1 and 2 in the midbrain development and dopaminergic neuron differentiation

Lines connect the coordinator with its partners. CORDIS does not always give exact coordinates for projects before 2014. These points are placed at city or country level.

Project objective

Patterning of midbrain and specification of the midbrain dopaminergic neurons is controlled by signalling molecules Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8). In embryogenesis, Fgf8 can transduce its signal via three Fgf receptors (Fgfr). W e want to find out whether Fgfr 1 and 2 are required for differentiation of the midbrain and the midbrain dopaminergic neurons.Our model is conditional inactivation of Fgr1 and 2 in mice. We will perform spatially and temporally controlled ablation of Fgf r1/2 genes in mutant mice as well as in ex vivo cultured midbrain explants using an inducible Cre recombinase, adenovirus mediated gene delivery and embryo electroporation. Consequently, we want to clarify molecular mechanisms of Fgf receptor mediated signalling. Morphogenesis is the consequence of subtly regulated balance between proliferation and differentiation.We suggest that Shh and Fgf8 direct the midbrain development by modulating expression of c-myc and or n-myc well-known regulators of proliferation and differentiation. C -myc/n-myc overexpression and siRNA-mediated gene silencing in wild type and Fgfrs mutant mice will be carried out to analyze the role of the myc genes in control proliferation/differentiation in midbrain.The study of dopaminergic neuronal specification and maintenance has significant clinical relevance, as it will advance our understanding of neuron's degeneration in Parkinson's disease and may offer therapeutical tools for the treatment of the ailment.

Original text from CORDIS.

Participants

• INSTITUTE OF BIOTECHNOLOGY, THE UNIVERSITY OF HELSINKICoordinatorCity levelFinland

Links

• View on CORDIS