Expression of Notch and Wnt pathway components and activation of Notch signaling in medulloblastomas from heterozygous patched mice.
Hedgehog (Hh), Notch, and Wingless (Wnt) signaling control normal development of the cerebellum, and dysregulation of these signaling pathways are associated with medulloblastoma (MB). As an initial step in the study of the role of interacting signaling pathways in MB pathogenesis, we demonstrate the expression of several components of the Notch and Wnt signaling pathways, and activation of Notch signaling in MB from Ptch +/- mice that have elevated Hh signaling. We also show a marked downregulation in the expression of Notch2, Jagged1, Hes1, mSfrp1, and mFrz7 in cerebella of developing mice with reduced Hh signaling, suggesting that Hh signaling regulates the expression of these genes. Together with recent published data, these findings indicate that Hh signaling might synergize simultaneously with Notch and Wnt signaling in MB development by controlling Notch and Wnt pathway ligand, receptor and/or target gene expression.
Dakubo
Gabriel D
GD
Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, K1H 8L6, Ottawa, ON, Canada. gabriel.dakubo@genesisgenomics.com
Mazerolle
Chantal J
CJ
Wallace
Valerie A
VA
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002528:Cerebellar Neoplasms / Q000378:metabolism*; D006579:Heterozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008527:Medulloblastoma / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*
D002352:Carrier Proteins; C498447:Hhip protein, mouse; D008562:Membrane Glycoproteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D051153:Wnt Proteins