title: RNA-seq analysis of developing olfactory bulb projection neurons.
abstract: Transmission of olfactory information to higher brain regions is mediated by olfactory bulb (OB) projection neurons, the mitral and tufted cells. Although mitral/tufted cells are often characterized as the OB counterpart of cortical projection neurons (also known as pyramidal neurons), they possess several unique morphological characteristics and project specifically to the olfactory cortices. Moreover, the molecular networks contributing to the generation of mitral/tufted cells during development are largely unknown. To understand the developmental patterns of gene expression in mitral/tufted cells in the OB, we performed transcriptome analyses targeting purified OB projection neurons at different developmental time points with next-generation RNA sequencing (RNA-seq). Through these analyses, we found 1202 protein-coding genes that are temporally differentially-regulated in developing projection neurons. Among them, 388 genes temporally changed their expression level only in projection neurons. The data provide useful resource to study the molecular mechanisms regulating development of mitral/tufted cells. We further compared the gene expression profiles of developing mitral/tufted cells with those of three cortical projection neuron subtypes, subcerebral projection neurons, corticothalamic projection neurons, and callosal projection neurons, and found that the molecular signature of developing olfactory projection neuron bears resemblance to that of subcerebral neurons. We also identified 3422 events that change the ratio of splicing isoforms in mitral/tufted cells during maturation. Interestingly, several genes expressed a novel isoform not previously reported. These results provide us with a broad perspective of the molecular networks underlying the development of OB projection neurons.
authors.affiliation: Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA; Institute for Personalized Medicine, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA.
authors.forename: Yuka Imamura
authors.initials: YI
authors.lastname: Kawasawa
authors.affiliation: Institute for Personalized Medicine, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Salzberg
authors.affiliation: Department of Neuroscience, Yale School of Medicine, 300 Cedar St., New Haven, CT 06510, USA.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neuroscience, Yale School of Medicine, 300 Cedar St., New Haven, CT 06510, USA; Kavli Institute for Neuroscience, Yale School of Medicine, 300 Cedar St., New Haven, CT 06510, USA.
authors.forename: Nenad
authors.initials: N
authors.lastname: Šestan
authors.affiliation: Department of Neuroscience, Yale School of Medicine, 300 Cedar St., New Haven, CT 06510, USA; Department of Neurosurgery, Yale School of Medicine, 300 Cedar St., New Haven, CT 06510, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Greer
authors.affiliation: Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA. Electronic address: fimamura@hmc.psu.edu.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Imamura
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D016366:Open Reading Frames; D059467:Transcriptome
keywords: Alternative splicing; Cell-type specific transcriptome; Mitral cell; Neuronal development; Olfactory bulb; Pyramidal neuron; RNA-seq