title: Expanding the power of recombinase-based labeling to uncover cellular diversity.
abstract: Investigating the developmental, structural and functional complexity of mammalian tissues and organs depends on identifying and gaining experimental access to diverse cell populations. Here, we describe a set of recombinase-responsive fluorescent indicator alleles in mice that significantly extends our ability to uncover cellular diversity by exploiting the intrinsic genetic signatures that uniquely define cell types. Using a recombinase-based intersectional strategy, these new alleles uniquely permit non-invasive labeling of cells defined by the overlap of up to three distinct gene expression domains. In response to different combinations of Cre, Flp and Dre recombinases, they express eGFP and/or tdTomato to allow the visualization of full cellular morphology. Here, we demonstrate the value of these features through a proof-of-principle analysis of the central noradrenergic system. We label previously inaccessible subpopulations of noradrenergic neurons to reveal details of their three-dimensional architecture and axon projection profiles. These new indicator alleles will provide experimental access to cell populations at unprecedented resolution, facilitating analysis of their developmental origin and anatomical, molecular and physiological properties.
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Plummer
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Irina Y
authors.initials: IY
authors.lastname: Evsyukova
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Sabrina D
authors.initials: SD
authors.lastname: Robertson
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Marchena
authors.affiliation: Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Tucker
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA patricia.jensen@nih.gov.
authors.forename: Patricia
authors.initials: P
authors.lastname: Jensen
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism; D002645:Chickens; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D045522:Recombinases / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D005456:Fluorescent Dyes; D045522:Recombinases; D049452:Green Fluorescent Proteins
keywords: Cre; Dre; Flp; Intersectional labeling; Norepinephrine