title: A novel Wnt5a-Frizzled4 signaling pathway mediates activity-independent dendrite morphogenesis via the distal PDZ motif of Frizzled 4.
abstract: The morphology of the dendritic tree is critical to neuronal function and neural circuit wiring. Several Wnt family members have been demonstrated to play important roles in dendrite development. However, the Wnt receptors responsible for mediating this process remain largely elusive. Using primary hippocampal neuronal cultures as a model system, we report that Frizzled4 (Fzd4), a member of the Fzd family of Wnt receptors, specifically signals downstream of Wnt5a to promote dendrite branching and growth. Interestingly, the less conserved distal PDZ binding motif of Fzd4, and not its conserved proximal Dvl-interacting PDZ motif, is required for mediating this effect. We further showed that Dvl signaled parallel to and independent of Fzd4 in promoting dendrite growth. Unlike most previously described pathways, Wnt5a/Fzd4 signaling promoted dendrite development in an activity-independent and autocrine fashion. Together, these results provide the first identification of a Wnt receptor for regulating dendrite development in the mammalian system, and demonstrate a novel function of the distal PDZ motif of Fzd4 in dendrite morphogenesis, thereby expanding our knowledge of the complex roles of Wnt signaling in neural development.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.|University of Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Bian
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Miao
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Shun-Ji
authors.initials: SJ
authors.lastname: He
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Zong-Fang
authors.initials: ZF
authors.lastname: Wan
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Zhen-Ge
authors.initials: ZG
authors.lastname: Luo
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D051157:Frizzled Receptors / Q000378:metabolism*; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; D051157:Frizzled Receptors; C498581:Fzd4 protein, mouse; C498582:Fzd4 protein, rat; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C491837:Wnt5a protein, rat; D051528:Guanylate Kinases
keywords: Frizzled4; PDZ motif; Wnt5a; activity-independent; dendrite development