title: Astrocyte-derived phosphatidic acid promotes dendritic branching.
abstract: Astrocytes play critical roles in neural circuit formation and function. Recent studies have revealed several secreted and contact-mediated signals from astrocytes which are essential for neurite outgrowth and synapse formation. However, the mechanisms underlying the regulation of dendritic branching by astrocytes remain elusive. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline, has been implicated in the regulation of neurite outgrowth. Here we showed that knockdown of PLD1 selectively in astrocytes reduced dendritic branching of neurons in neuron-glia mixed culture. Further studies from sandwich-like cocultures and astrocyte conditioned medium suggested that astrocyte PLD1 regulated dendritic branching through secreted signals. We later demonstrated that PA was the key mediator for astrocyte PLD1 to regulate dendritic branching. Moreover, PA itself was sufficient to promote dendritic branching of neurons. Lastly, we showed that PA could activate protein kinase A (PKA) in neurons and promote dendritic branching through PKA signaling. Taken together, our results demonstrate that astrocyte PLD1 and its lipid product PA are essential regulators of dendritic branching in neurons. These results may provide new insight into mechanisms underlying how astrocytes regulate dendrite growth of neurons.
authors.affiliation: Laboratories of Stem Cell Biology and Regenerative Medicine, Department of Neurology, Experimental Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yan-Bing
authors.initials: YB
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Gao
authors.affiliation: Laboratories of Stem Cell Biology and Regenerative Medicine, Department of Neurology, Experimental Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jia
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Xue-Fang
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Yin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015415:Biomarkers; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D009474:Neurons / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D010712:Phosphatidic Acids; D017868:Cyclic AMP-Dependent Protein Kinases; D010739:Phospholipase D; C106801:phospholipase D1