Of the hh homologues, SHH has been found to have the most critical roles in development, acting as a morphogen involved in patterning many systems, including the anterior pituitary, pallium of the brain, spinal cord, lungs, teeth, and the thalamus by the zona limitans intrathalamica. In vertebrates, the development of limbs and digits depends on the secretion of sonic hedgehog by the zone of polarizing activity, located on the posterior side of the embryonic limb bud. Mutations in the human sonic hedgehog gene, SHH, cause holoprosencephaly type 3 HPE3 as a result of the loss of the ventral midline. The sonic hedgehog transcription pathway has also been linked to the formation of specific kinds of cancerous tumors, including the embryonic cerebellar tumor, and medulloblastoma, as well as the progression of prostate cancer tumours. For SHH to be expressed in the developing embryo limbs, a morphogen called fibroblast growth factors must be secreted from the apical ectodermal ridge.