title: Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.
abstract: Auditory information is initially processed in the cochlear nuclei before being relayed to the brain. The cochlear nuclei are subdivided into dorsal, anterior ventral, and posterior ventral domains, each containing several subtypes of neurons that are thought to play discrete roles in the processing of sound. However, the ontogeny of these neurons is poorly understood, and this gap in knowledge hampers efforts to understand the basic neural circuitry of this nucleus. Here, we reveal that Bhlhb5 is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the DCN during development. To gain genetic access to Bhlhb5-expressing neurons in the DCN, we generated a Bhlhb5::flpo knockin allele. Using an intersectional genetic strategy, we labeled cartwheel cells, thereby providing proof of concept that subpopulations of Bhlhb5-expressing neurons can be genetically targeted. Moreover, fate-mapping experiments using this allele revealed that Bhlhb5 is required for the proper development of the DCN, since mice lacking Bhlhb5 showed a dramatically diminished number of neurons, including unipolar brush and cartwheel cells. Intriguingly, the Bhlhb5::flpo allele also genetically labels numerous other regions of the nervous system that process sensory input, including the dorsal horn, the retina, and the nucleus of the lateral olfactory tract, hinting at a more general role for Bhlhb5 in the development of neurons that mediate sensory integration.
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; The Pittsburgh Center for Pain Research, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; The Pittsburgh Center for Pain Research, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Kardon
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; The Pittsburgh Center for Pain Research, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Snyder
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; The Pittsburgh Center for Pain Research, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Marissa S
authors.initials: MS
authors.lastname: Kuzirian
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Minestro
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Luiza
authors.initials: L
authors.lastname: de Souza
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rubio
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Maricich
authors.affiliation: Department of Neurobiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; The Pittsburgh Center for Pain Research, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA. Electronic address: saross@pitt.edu.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ross
mesh_terms: D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D019070:Cell Lineage; D017626:Cochlear Nucleus / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009830:Olfactory Bulb / Q000378:metabolism; D000071841:PAX6 Transcription Factor / Q000378:metabolism; D020671:Posterior Horn Cells / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008164:Luminescent Proteins; D000071841:PAX6 Transcription Factor; C488357:Bhlhe22 protein, mouse
keywords: Bhlhb5; Bhlhe22; Cre recombinase; Dorsal cochlear nucleus; Flp recombinase