Human developmental disorders and the Sonic hedgehog pathway.
Sonic hedgehog (Shh) is a morphogen that is crucial for normal development of a variety of organ systems, including the brain and spinal cord, the eye, craniofacial structures, and the limbs. Mutations in the human SHH gene and genes that encode its downstream intracellular signaling pathway cause several clinical disorders. These include holoprosencephaly (HPE, the most common anomaly of the developing forebrain), nevoid basal cell carcinoma syndrome, sporadic tumors, including basal cell carcinomas, and three distinct congenital disorders: Greig syndrome 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 of the SHH pathway in human development.
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
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JE
Ming
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Roessler
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Muenke
D000818:Animals; D001478:Basal Cell Nevus Syndrome / Q000209:etiology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D006130:Growth Disorders / Q000235:genetics; D053823:Hedgehog Proteins; D016142:Holoprosencephaly / Q000209:etiology; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011506:Proteins; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3