Genetic modulation of horizontal cell number in the mouse retina

Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9697-702. doi: 10.1073/pnas.1103253108. Epub 2011 May 16.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Cell Count
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Follistatin / genetics
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics*
  • LIM-Homeodomain Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Promoter Regions, Genetic / genetics
  • Quantitative Trait Loci / genetics
  • Retina / cytology
  • Retina / embryology
  • Retina / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors


  • 5' Untranslated Regions
  • Follistatin
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1