Development, Vol 126, Issue 14 3089-3100, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

Sonic hedgehog regulates the growth and patterning of the cerebellum

N Dahmane and A Ruiz-i-Altaba
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

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.
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				T. Sakurai, M. Lustig, J. Babiarz, A. J.W. Furley, S. Tait, P. J. Brophy, S. A. Brown, L. Y. Brown, C. A. Mason, and M. Grumet Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development J. Cell Biol., September 17, 2001; 154(6): 1259 - 1274. [Abstract] [Full Text] [PDF]

				J. Ko, S. Humbert, R. T. Bronson, S. Takahashi, A. B. Kulkarni, E. Li, and L.-H. Tsai p35 and p39 Are Essential for Cyclin-Dependent Kinase 5 Function during Neurodevelopment J. Neurosci., September 1, 2001; 21(17): 6758 - 6771. [Abstract] [Full Text] [PDF]

				Q. R. Lu, J. K. Park, E. Noll, J. A. Chan, J. Alberta, D. Yuk, M. G. Alzamora, D. N. Louis, C. D. Stiles, D. H. Rowitch, et al. Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors PNAS, August 23, 2001; (2001) 181340798. [Abstract] [Full Text] [PDF]

				T. Yamasaki, K. Kawaji, K. Ono, H. Bito, T. Hirano, N. Osumi, and M. Kengaku Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum Development, August 15, 2001; 128(16): 3133 - 3144. [Abstract] [Full Text] [PDF]

				R. S. Klein, J. B. Rubin, H. D. Gibson, E. N. DeHaan, X. Alvarez-Hernandez, R. A. Segal, and A. D. Luster SDF-1{alpha} induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells Development, June 1, 2001; 128(11): 1971 - 1981. [Abstract] [Full Text] [PDF]

				E. A. Maher, F. B. Furnari, R. M. Bachoo, D. H. Rowitch, D. N. Louis, W. K. Cavenee, and R. A. DePinho Malignant glioma: genetics and biology of a grave matter Genes & Dev., June 1, 2001; 15(11): 1311 - 1333. [Full Text] [PDF]

				S Pons, J. Trejo, J. Martinez-Morales, and E Marti Vitronectin regulates Sonic hedgehog activity during cerebellum development through CREB phosphorylation Development, January 5, 2001; 128(9): 1481 - 1492. [Abstract] [PDF]

				X. Zhang and X. Yang Regulation of retinal ganglion cell production by Sonic hedgehog Development, January 3, 2001; 128(6): 943 - 957. [Abstract] [PDF]

				A. M. Kenney and D. H. Rowitch Sonic hedgehog Promotes G1 Cyclin Expression and Sustained Cell Cycle Progression in Mammalian Neuronal Precursors Mol. Cell. Biol., December 1, 2000; 20(23): 9055 - 9067. [Abstract] [Full Text]

				K. Miyazawa, T. Himi, V. Garcia, H. Yamagishi, S. Sato, and Y. Ishizaki A Role for p27/Kip1 in the Control of Cerebellar Granule Cell Precursor Proliferation J. Neurosci., August 1, 2000; 20(15): 5756 - 5763. [Abstract] [Full Text] [PDF]

				C. Wetmore, D. E. Eberhart, and T. Curran The Normal patched Allele Is Expressed in Medulloblastomas from Mice with Heterozygous Germ-Line Mutation of patched Cancer Res., April 1, 2000; 60(8): 2239 - 2246. [Abstract] [Full Text]

				R Brewster, J. Mullor, and A Ruiz i Altaba Gli2 functions in FGF signaling during antero-posterior patterning Development, January 10, 2000; 127(20): 4395 - 4405. [Abstract] [PDF]

				D. S. Rice and T. Curran Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS Genes & Dev., November 1, 1999; 13(21): 2758 - 2773. [Full Text]