title: The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development.
abstract: In the mouse retina, at least ten distinct types of bipolar interneurons are involved in the transmission of visual signals from photoreceptors to ganglion cells. How bipolar interneuron diversity is generated during retinal development is poorly understood. Here, we show that Irx5, a member of the Iroquois homeobox gene family, is expressed in developing bipolar cells starting at postnatal day 5 and is localized to a subset of cone bipolar cells in the mature mouse retina. In Irx5-deficient mice, defects were observed in the expression of some, but not all, immunohistological markers that define mature Type 2 and Type 3 OFF cone bipolar cells, indicating a role for Irx5 in bipolar cell differentiation. The differentiation of these two bipolar cell types has previously been shown to require the homeodomain-CVC transcription factor, Vsx1. However, the defects observed in Irx5-deficient retinas do not coincide with a reduction of Vsx1 expression, and conversely, the expression of Irx5 in cone bipolar cells does not require the presence of a functional Vsx1 allele. These results indicate that there are at least two distinct genetic pathways (Irx5-dependent and Vsx1-dependent) regulating the development of Type 2 and Type 3 cone bipolar cells.
authors.affiliation: Program in Developmental Biology, The Hospital for Sick Children, and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Chi Wa
authors.initials: CW
authors.lastname: Cheng
authors.forename: Robert L
authors.initials: RL
authors.lastname: Chow
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lebel
authors.forename: Rui
authors.initials: R
authors.lastname: Sakuma
authors.forename: Helen Oi-Lam
authors.initials: HO
authors.lastname: Cheung
authors.forename: Vijitha
authors.initials: V
authors.lastname: Thanabalasingham
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
authors.forename: David G
authors.initials: DG
authors.lastname: Birch
authors.forename: Chi-chung
authors.initials: CC
authors.lastname: Hui
authors.forename: Roderick R
authors.initials: RR
authors.lastname: McInnes
authors.forename: Shuk Han
authors.initials: SH
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D005136:Eye Proteins / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000502:physiology; D012160:Retina / Q000196:embryology*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C501601:Irx5 protein, mouse; D014157:Transcription Factors; C491582:Vsx1 protein, mouse