Figure 5. Mechanism of RMS formation in heterozygous Ptch mice.

Initially the Ptch promoter is not methylated during early embryonic development allowing abundant expression (thick arrows) of wildtype (wt) and mutant (mut) Ptch transcripts in heterozygous Ptch knockout mice. Subsequently methylation (resembled by lollipops) of the Ptch promoter starts at E13.5 or later during embryogenesis leading to decreased Ptch expression of the methylated alleles (as indicated by thin arrows). If both Ptch alleles are methylated myogenesis proceeds unperturbed and wt as well as mut Ptch are expressed at low levels during and after myogenesis (indicated by grey color). If the mut allele remains accidentally unmethylated and Gli1 binding is increased, the cell of origin for RMS (single black cell) expresses high levels of mut Ptch (indicated by black color) and finally gives rise to RMS (cluster of black cells) during adulthood.