Cerebellar granule cells: insights into proliferation, differentiation, and role in medulloblastoma pathogenesis

Cerebellar granule cells originate from precursors located in the dorsal region of rhombomere one within the hindbrain of developing embryos. They undergo proliferation for an extensive period well into postnatal stages of development to form the major cell type of the cerebellum, the most populous structure within the mammalian brain. Granule cell development is highly dependent upon the cerebellar environment and contact with neighbouring cells. In recent years, the molecular basis of these interactions has started to be unravelled. Granule cell precursors and the molecular mechanisms involved in controlling their proliferation have been shown to be involved in the pathogenesis of medulloblastoma, the most common malignant pediatric brain tumour. Here, we review the control of granule cell generation with emphasis on the molecular regulators of cell proliferation and differentiation during normal and malignant development.     

The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup

Background  

Polarised gene expression is thought to lead to the graded distribution of signaling molecules providing a patterning mechanism across the embryonic eye. Bone morphogenetic protein 4 (Bmp4) is expressed in the dorsal optic vesicle as it transforms into the optic cup. Bmp4 deletions in human and mouse result in failure of eye development, but little attempt has been made to investigate mammalian targets of BMP4 signaling. In chick, retroviral gene overexpression studies indicate that Bmp4 activates the dorsally expressed Tbx5 gene, which represses ventrally expressed cVax. It is not known whether the Tbx5 related genes, Tbx2 and Tbx3, are BMP4 targets in the mammalian retina and whether BMP4 acts at a distance from its site of expression. Although it is established that Drosophila Dpp (homologue of vertebrate Bmp4) acts as a morphogen, there is little evidence that BMP4 gradients are interpreted to create domains of BMP4 target gene expression in the mouse.