title: Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development.
abstract: Dendrite size and morphology are key determinants of the functional properties of neurons. Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor β superfamily with a well-characterised role in limb morphogenesis, is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. Pyramidal cells co-express GDF5 and its preferred receptors, BMP receptor 1B and BMP receptor 2, during development. In culture, GDF5 substantially increased dendrite, but not axon, elongation from these neurons by a mechanism that depends on activation of SMADs 1/5/8 and upregulation of the transcription factor HES5. In vivo, the apical and basal dendritic arbours of pyramidal cells throughout the hippocampus were markedly stunted in both homozygous and heterozygous Gdf5 null mutants, indicating that dendrite size and complexity are exquisitely sensitive to the level of endogenous GDF5 synthesis.
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AT, UK.
authors.forename: Catarina
authors.initials: C
authors.lastname: Osório
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Chacón
authors.forename: Lilian
authors.initials: L
authors.lastname: Kisiswa
authors.forename: Matthew
authors.initials: M
authors.lastname: White
authors.forename: Sean
authors.initials: S
authors.lastname: Wyatt
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rodríguez-Tébar
authors.forename: Alun M
authors.initials: AM
authors.lastname: Davies
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D055428:Growth Differentiation Factor 5 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017966:Pyramidal Cells / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D055428:Growth Differentiation Factor 5; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; C525894:Gdf5 protein, mouse; C489685:Hes5 protein, mouse; C497401:Smad1 protein, mouse; C497798:Smad5 protein, mouse; C491621:Smad9 protein, mouse; C498215:Bmpr1b protein, mouse; C498219:Bmpr2 protein, mouse
keywords: Bone morphogenetic protein; Dendrite; Growth differentiation factor 5; Hippocampus; Mouse