Integration of Growth Factor Signals Regulating Cellular Differentiation in Embryonic Midbrain-hindbrain Region

Principal Investigators: JUHA PARTANEN1, JUSSI TAIPALE1, TIMOTHY HUGHES2

1University of Helsinki, Finland, 2University of Toronto, Canada

Dopaminergic and serotonergic neurons, which develop in the embryonic midbrain-hindbrain region, are playing a central role in regulation of motor functions as well as mood, reward and addiction. Development of these neurons during embryogenesis is determined by concentrations of multiple intercellular signaling molecules. The extracellular gradients of the signaling molecules are converted into intracellular gradients of specific transcription factors, which then combinatorially regulate gene-expression and specify distinct neuronal subtypes. However, the mechanism by which the different transcription factors then combinatorially specify distinct neuronal subtypes is not understood. 

We propose to characterize in detail how the three growth factor families, FGF, Wnt and Hedgehog, regulate neuronal development in the midbrain-hindbrain region during mouse embryonic development. We will use spatially and temporally controlled mutagenesis in mice. To understand how these signals are integrated, we will analyze the transcriptional target genes of the pathways in the midbrain and hindbrain using recently developed biochemical and bioinformatics tools. Further functional characterization of such combinatorial target genes is expected to reveal how cells integrate the different growth factor signals in vivo and differentiate into specific types of neurons.

Contact: juha.m.partanen(at)helsinki.fi, tel. +358 9 1915 9382