title: Genetic modulation of horizontal cell number in the mouse retina.
abstract: Neuronal populations display conspicuous variability in their size among individuals, but the genetic sources of this variation are largely undefined. We demonstrate a large and highly heritable variation in neuron number within the mouse retina, affecting a critical population of interneurons, the horizontal cells. Variation in the size of this population maps to the distal end of chromosome (Chr) 13, a region homologous to human Chr 5q11.1-11.2. This region contains two genes known to modulate retinal cell number. Using conditional knock-out mice, we demonstrate that one of these genes, the LIM homeodomain gene Islet-1 (Isl1), plays a role in regulating horizontal cell number. Genetic differences in Isl1 expression are high during the period of horizontal cell production, and cis-regulation of Isl1 expression within the retina is demonstrated directly. We identify a single nucleotide polymorphism in the 5' UTR of Isl1 that creates an E-box sequence as a candidate causal variant contributing to this variation in horizontal cell number.
authors.affiliation: Neuroscience Research Institute and Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Whitney
authors.forename: Mary A
authors.initials: MA
authors.lastname: Raven
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Ciobanu
authors.forename: Ross A
authors.initials: RA
authors.lastname: Poché
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.forename: Yasser
authors.initials: Y
authors.lastname: Elshatory
authors.forename: Lin
authors.initials: L
authors.lastname: Gan
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reese
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D002452:Cell Count; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D038681:Follistatin / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors
chemical_list: D020121:5' Untranslated Regions; D038681:Follistatin; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1