The overall goal of this project is to examine the control of granule neuron specification and differentiation in embryonic stages of vertebrate cerebellar development. In the first group of experiments, expression of the zinc finger transcription factor RU49 will be used to map the earliest granule precursors in the midbrain/hindbrain region of mouse embryos ib embryonic days 9.5 through 13.5. The second set of experiments will localize expression of the TGFbeta family of growth factors (BMP6, BMP7 or GDF7) in the midbrain/hindbrain region of the neural tube, and test the role of these factors in induction of RU49. In a third set of experiments, the role of the basic helix loop helix transcription factor Math-1 (atonal) in EGL cell specification and differentiation will be studied Expression of Math-1 will be defined in situ hybridization of mRNAs in vivo between E8.0 and p15, as well as in cultures of purified progenitor cells and the function of Math-1 will be investigated by over-expression of the gene and by expression of a dominant negative form of the gene. In a fourth group of experiments, video microscopy will be used to define the mitotic activity and mode of movement of progenitor cells within the rhombic lip cells during the initial steps of the formation of the external germinal layer (EGL). The relationship between cell division and movement of cells onto the surface of the cerebellar anlage will be examined by tracing dye-labeled cells in explants of embronic midbrain/hindbrain tissue. The behavior of cells in the rhombic lip will be compared among three vertebrates: Mus musculis, Gallus domesticus and Xenopus laevis.
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