Even cancers want commitment: lineage identity and medulloblastoma formation

Abstract

In this issue of Cancer Cell, Yang et al. (2008) and Schüller et al. (2008) show that Hedgehog activation in either multipotent neural stem cells or developmentally restricted progenitors causes only medulloblastomas to form. These data suggest that some stem cell-derived tumors must commit to a specific lineage in order to grow.

Figure 1. Hedgehog-Induced Medulloblastoma in Multipotent and Lineage-Restricted Cerebellar Cells

Multipotent cells expressing GFAP or Olig2 populate the fetal cerebellar ventricular zone and give rise to Purkinje cells, Bergmann glia, astrocytes, and oligodendrocytes. They also generate granule neuron precursors (GNP) in the rhombic lip that migrate over the cerebellar surface to form an external germinal layer of progenitors committed to differentiate into granule neurons. Activating Hedgehog signaling in either multipotent stem cells or GNPs results in the formation of medulloblastomas (MB) that express markers of granule neuron differentiation, but not tumors resembling other glial or neuronal cell types. Activation of Hedgehog in Purkinje cells fails to generate tumors.