Functional relevance of Tgfß-signalling for the development of the certebral cortex
Transforming growth factor β (Tgfβ) mediated neurogenesis has been reported to be increased in older (E16.5) embryonic cortical progenitor cells as compared to that in E13.5 and adult spheres. In this project we aim to reveal key genes that highlight what function Tgfβ-signalling mediates during cortical and hippocampal development and how Tgfβ affects neurogenesis in an age-dependent manner. We are using microarrays with RNA extracted from Tgfβ-treated primary cortical cells from different embryonic stages. Clusters of regulated genes that are categorized into genes affecting neuronal differentiation, proliferation, apoptosis, transcription factors and genes expressed in the extracellular matrix which are validated for regulations through Tgfβ via semiquantitative and qRT-PCR, as well as in situ hybridizations and immunohistochemical stainings in mutant mice with defects of Tgfβ-signalling at different levels. Virus-mediated overexpression and siRNA-mediated knock down of Tgfβ-target genes will complete our efforts to shed further light into the role of Tgfβ for cortical development. We are also aiming to investigate whether cross talk with other signalling pathways, such as IGF-signalling, modulates the context-dependent response of neural progenitors to Tgfβ-signalling. Embryonic stem cells and primary neural progenitor cells are used to explore SMAD-dependent signal transduction and its different read-outs on transcriptional levels.
Ansprechpartner: Prof. Dr. Tanja Vogel