title: Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice.
abstract: BACKGROUND
  BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid-releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5's functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas.
  
  
  RESULTS
  In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells.
  
  
  CONCLUSIONS
  Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes.
authors.affiliation: Medical College of Nanchang University, Nanchang, Jiangxi, China; Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China; First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, China; Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Xiong-Jian
authors.initials: XJ
authors.lastname: Luo
authors.forename: Guoqing
authors.initials: G
authors.lastname: Liang
authors.forename: Xiang-Yun
authors.initials: XY
authors.lastname: Zeng
authors.forename: Jing-Lin
authors.initials: JL
authors.lastname: Yi
authors.forename: Lin
authors.initials: L
authors.lastname: Gan
mesh_terms: D025042:Amacrine Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006652:Histological Techniques; D007150:Immunohistochemistry; D051379:Mice; D012160:Retina / Q000166:cytology* / Q000254:growth & development; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; C488357:Bhlhe22 protein, mouse
keywords: Bhlhb5; amacrine cell; bipolar cell; neurogenesis; retina; transcription factor