The Hedgehog-Gli signaling pathway is involved in the regulation of the 
proliferation of precursors in different organs of the normal vertebrate embryo. 
These cells express Gli1 and may be the target of cancer-causing agents. Many 
tumor types derived from organs that contain Gli1+ precursors appear to 
consistently express Gli1, indicating their origin and/or the presence of an 
active pathway. Inappropriate pathway activation in a variety of precursor cells 
in model organisms leads to tumor formation while inhibition of the pathway in 
human tumor cells leads to a decrease in their proliferation. In the brain we 
have documented the expression of Gli1 in germinative zones, and a variety of 
brain tumors express GLI1, including medulloblastomas of the cerebellum and a 
number of gliomas of the cerebral cortex. The requirement for SHH-Gli signaling 
in the growth of the mouse brain, together with the ability of inappropriate 
pathway activation in the cerebellum to cause medulloblastomas, and the 
inhibition of the growth of a number of brain tumors with cyclopamine, a SHH 
signaling inhibitor, underscores the critical role of the SHH-GLI pathway in 
brain growth and tumor formation. Moreover, they highlight the components of 
this pathway as prime targets for drug development, with special emphasis on the 
GLI proteins. Such reagents would allow a rational therapeutic approach to 
highly intractable diseases.