title: Expression of Sonic hedgehog during cell proliferation in the human cerebellum.
abstract: The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL. Deregulation of Shh signaling has been associated with abnormal development, and been implicated in medulloblastomas, which are tumors that arise from the cerebellum. Given the importance of the Shh pathway in cerebellum development and disease, there has been no systematic study of its expression pattern during human cerebellum development. In this study, we describe the expression pattern of Shh, its receptor patched, smoothened, and its effectors that belong to the Gli family of transcription factors, during normal human cerebellum development from 10 weeks of gestational age, and in medulloblastomas that represents a case of abnormal cell proliferation in the cerebellum. This expression pattern is compared to equivalent stages in the normal development of cerebellum in mouse, as well as in tumors. Important differences between human and mouse that reflect differences in the normal developmental program between the 2 species are observed. First, in humans there appears to be a stage of Shh signaling within the EGL, when the PC are not yet the source of Shh. Second, unlike in the postnatal mouse cerebellum, expression of Shh in the PC in the postnatal human cerebellum is downregulated. Finally, medulloblastomas in the human but not in patched heterozygote mouse express Shh. These results highlight cross-species differences in the regulation of the Shh signaling pathway.
authors: National Brain Research Centre, Manesar, India.
authors: Parthiv
authors: P
authors: Haldipur
authors: Upasna
authors: U
authors: Bharti
authors: Subashika
authors: S
authors: Govindan
authors: Chitra
authors: C
authors: Sarkar
authors: Soumya
authors: S
authors: Iyengar
authors: Pierre
authors: P
authors: Gressens
authors: Shyamala
authors: S
authors: Mani
mesh_terms: D000818:Animals; D064026:Calbindins; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D002675:Child, Preschool; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072079:Patched Receptors; D011689:Purkinje Cells / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: D064026:Calbindins; C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D064030:S100 Calcium Binding Protein G; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2