Figure 2.

Atoh1-cre induced overexpression of smoothened (smo) results in a rapid growth of MB (B) in mice. Control littermates have a drastically smaller and highly differentiated cerebellum (A). The size of the MB in mice expressing Neurod1 (F) was indistinguishable from simple smoothened overexpresser, indicating that Neurod1 expressed off the Rosa26 locus does not suffice to alter the fate after Atoh1-cre induced constitutively active smo. Reducing the Atoh1 level in combination with expression of Neurod1 from the Rosa26 locus has only minor effects on overall cerebellar development (note the reduction in lob size and in particular loss of sublobes in D compared to C). Reducing Atoh1 while expressing constitutively active smo with (F) or without (E) Neurod1 causes slower MB formation through transformation of the embryonic external granular layer. However, this transformation extends only in mice without Neurod1 into lobes with late expression of the Atoh1-cre transgene (IX and X). Comparing lobe IX with or without Neurod1 (arrow in E,F) shows reduced transformation of external granular cell layer into MB. Details of central lobes show that overexpression of Neurod1 has no major defect (G, I) but affects tumor progression by allowing some external granular cells to variably migrate to the internal granular layer. Scale bars indicate 1mm in A-F and100 μm in G-J.