title: Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling.
abstract: Mitral cells (MCs) of the mammalian olfactory bulb have a single primary dendrite extending into a single glomerulus, where they receive odor information from olfactory sensory neurons (OSNs). Molecular mechanisms for controlling dendritic arbors of MCs, which dynamically change during development, are largely unknown. Here we found that MCs displayed more complex dendritic morphologies in mouse mutants of Maml1, a crucial gene in Notch signaling. Similar phenotypes were observed by conditionally misexpressing a dominant negative form of MAML1 (dnMAML1) in MCs after their migration. Conversely, conditional misexpression of a constitutively active form of Notch reduced their dendritic complexity. Furthermore, the intracellular domain of Notch1 (NICD1) was localized to nuclei of MCs. These findings suggest that Notch signaling at embryonic stages is involved in the dendritic complexity of MCs. After the embryonic misexpression of dnMAML1, many MCs aberrantly extended dendrites to more than one glomerulus at postnatal stages, suggesting that Notch signaling is essential for proper formation of olfactory circuits. Moreover, dendrites in cultured MCs were shortened by Jag1-expressing cells. Finally, blocking the activity of Notch ligands in OSNs led to an increase in dendritic complexity as well as a decrease in NICD1 signals in MCs. These results demonstrate that the dendritic complexity of MCs is controlled by their presynaptic partners, OSNs.
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuko
authors.identifier: http://orcid.org/0000-0002-6697-2123
authors.initials: Y
authors.lastname: Muroyama
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Atsushi
authors.identifier: http://orcid.org/0000-0002-6871-7249
authors.initials: A
authors.lastname: Baba
authors.affiliation: Department of Molecular and Tumor Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Motoo
authors.identifier: http://orcid.org/0000-0003-1036-840X
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000072100:Jagged-1 Protein / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D009830:Olfactory Bulb / Q000254:growth & development / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C486455:Maml1 protein, mouse; C497762:Notch1 protein, mouse; D009687:Nuclear Proteins; D051881:Receptor, Notch1; D014157:Transcription Factors