FIGURE 2.

Schematic representation of cerebellar development and initiation of MB_SHH. During the postnatal stage, GCPs normally proliferate in the outer edge of the EGL under the regulation of SHH secreted by the Purkinje cells. GCPs exit the cell cycle and subsequently migrate radially, toward the IGL, to mature into the iEGL. Somatic genetic mutations often cause aberrant SHH signaling that results in a failure to exit the cell cycle, leading to hyperproliferation. Abnormal differentiation of GCPs induces the formation of preneoplastic lesion and MB_SHHs predominantly on the surface of the cerebellar hemispheres (bottom right). Please note that the locations of other subtypes of MBs, such as MB_WNTs and MB_Grp3/4s, are distinct from that of MB_SHHs (Kawauchi et al., 2017), implying distinct cellular origins of these subgroups. GCP, granule cell precursor; oEGL, outer external granular layer; iEGL, inner external granular layer; ML, molecular layer; PCL, purkinje cell layer. IGL, internal granular layer.