title: Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
abstract: Signals that govern development of the osteoblast lineage are not well understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins, is essential for osteogenesis in the endochondral skeleton during embryogenesis. The canonical pathway of Wnt signaling has been implicated by studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass homeostasis. In the present study we demonstrate that beta-catenin, a central player in the canonical Wnt pathway, is indispensable for osteoblast differentiation in the mouse embryo. Moreover, we present evidence that Wnt signaling functions downstream of Ihh in development of the osteoblast lineage. Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development.
authors.affiliation: Department of Medicine, Washington University Medical School, St. Louis, MO 63110, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Hu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hilton
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Tu
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
authors.forename: Fanxin
authors.initials: F
authors.lastname: Long
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D026502:LDL-Receptor Related Proteins; D008024:Ligands; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins; D008024:Ligands; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D015534:Trans-Activators; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse; D051176:beta Catenin