title: En1 directs superior olivary complex neuron positioning, survival, and expression of FoxP1.
abstract: Little is known about the genetic pathways and transcription factors that control development and maturation of central auditory neurons. En1, a gene expressed by a subset of developing and mature superior olivary complex (SOC) cells, encodes a homeodomain transcription factor important for neuronal development in the midbrain, cerebellum, hindbrain and spinal cord. Using genetic fate-mapping techniques, we show that all En1-lineal cells in the SOC are neurons and that these neurons are glycinergic, cholinergic and GABAergic in neurotransmitter phenotype. En1 deletion does not interfere with specification or neural fate of these cells, but does cause aberrant positioning and subsequent death of all En1-lineal SOC neurons by early postnatal ages. En1-null cells also fail to express the transcription factor FoxP1, suggesting that FoxP1 lies downstream of En1. Our data define important roles for En1 in the development and maturation of a diverse group of brainstem auditory neurons.
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Altieri
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Walid
authors.initials: W
authors.lastname: Jalabi
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Tianna
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Romito-DiGiacomo
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA; Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA. Electronic address: stephen.maricich@chp.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Maricich
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D053144:Cell Nucleus Shape; D002470:Cell Survival; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D065832:Superior Olivary Complex / Q000166:cytology*
chemical_list: C080330:En1 protein, mouse; D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D018398:Homeodomain Proteins; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D018377:Neurotransmitter Agents; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors
keywords: Auditory; Brainstem; Deafness; Hearing; Nucleogenesis