SHH pathway and cerebellar development.
The morphogenetic factor Sonic hedgehog (SHH) has been discovered as one of the masterplayers in cerebellar patterning and was subjected to intensive investigation during the last decade. During early postnatal development, this continuously secreted cholesterol-modified protein drives the expansion of the largest neuronal population of the brain, the granular cells. Moreover, it acts on Bergmann glia differentiation and would potentially affect Purkinje cells homeostasis at adult age. The cerebellar cortex constituted an ideal developmental model to dissect out the upstream mechanisms and downstream targets of this complex pathway. Its deep understanding discloses some of the mechanistic disorders underlying pediatric tumorigenesis, congenital ataxia, and mental retardation. Therapeutical use of its regulators has been consolidated on murine transgenic models and is now considered as a realistic human clinical application. Here, we will review the most recent advances made in the comprehensive understanding of SHH involvement in cerebellar development and pathology.
Vaillant
Catherine
C
Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.
Monard
Denis
D
D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D053823:Hedgehog Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*
D053823:Hedgehog Proteins