Sonic hedgehog regulates the growth and patterning of the cerebellum.
The molecular bases of brain development and CNS malignancies remain poorly understood. Here we show that Sonic hedgehog (Shh) signaling controls the development of the cerebellum at multiple levels. SHH is produced by Purkinje neurons, it is required for the proliferation of granule neuron precursors and it induces the differentiation of Bergmann glia. Blocking SHH function in vivo results in deficient granule neuron and Bergmann glia differentiation as well as in abnormal Purkinje neuron development. Thus, our findings provide a molecular model for the growth and patterning of the cerebellum by SHH through the coordination of the development of cortical cerebellar cell types. In addition, they provide a cellular context for medulloblastomas, childhood cancers of the cerebellum.
Dahmane
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The Skirball Institute, Developmental Genetics Program and Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA. ria@saturn.med.nyu.edu
Ruiz i Altaba
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D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019521:Body Patterning / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development / Q000473:pathology*; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
D000906:Antibodies; D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C000618551:Gli2 protein, mouse; 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; C492123:ZIC1 protein, human; C492122:Zic1 protein, mouse; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3