title: Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity.
abstract: The neocortex contains diverse populations of excitatory neurons segregated by layer and further definable by their specific cortical and subcortical projection targets. The current study describes a systematic approach to identify molecular correlates of specific projection neuron classes in mouse primary somatosensory cortex (S1), using a combination of in situ hybridization (ISH) data mining, marker gene colocalization, and combined retrograde labeling with ISH for layer-specific marker genes. First, we identified a large set of genes with specificity for each cortical layer, and that display heterogeneous patterns within those layers. Using these genes as markers, we find extensive evidence for the covariation of gene expression and projection target specificity in layer 2/3, 5, and 6, with individual genes labeling neurons projecting to specific subsets of target structures. The combination of gene expression and target specificity imply a great diversity of projection neuron classes that is similar to or greater than that of GABAergic interneurons. The covariance of these 2 phenotypic modalities suggests that these classes are both discrete and genetically specified.
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Staci A
authors.initials: SA
authors.lastname: Sorensen
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Vilas
authors.initials: V
authors.lastname: Menon
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Royall
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Glattfelder
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Tsega
authors.initials: T
authors.lastname: Desta
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Hirokawa
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Marty
authors.initials: M
authors.lastname: Mortrud
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Hongkui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Hohmann
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Jones
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98040, USA.
authors.forename: Ed S
authors.initials: ES
authors.lastname: Lein
mesh_terms: D000818:Animals; D001271:Atlases as Topic; D057225:Data Mining; D015870:Gene Expression / Q000502:physiology; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D056325:Neuronal Tract-Tracers; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D013003:Somatosensory Cortex / Q000166:cytology* / Q000502:physiology*
chemical_list: D056325:Neuronal Tract-Tracers
keywords: cortical cell type; in situ hybridization; projection neuron; retrograde labeling; target specificity