HUMAN DEVELOPMENTAL DISORDERS AND THE SONIC HEDGEHOG PATHWAY

Sonic hedgehog (Shh) is a morphogen that is crucial for normal develop ment of a variety of organ systems, including the brain and spinal cor d, the eye, craniofacial structures, and the limbs, Mutations in the h uman SHH gene and genes that encode its downstream Intracellular signa ling pathway cause several clinical disorders, These include holoprose ncephaly (HPE, the most common anomaly of the developing forebrain), n evoid basal cell carcinoma syndrome, sporadic tumors, including basal cell carcinomas, and three distinct congenital disorders: Greig syndro me Pallister-Hall syndrome, and isolated postaxial polydactyly, These conditions caused by abnormalities in the SHH pathway demonstrate the crucial role of SHH in complex developmental processes, and molecular analyses of these disorders provide insight into the normal function o f the SHH pathway in human development.