Transdifferentiation of the retina into pigmented cells in ocular retardation mice defines a new function of the homeodomain gene Chx10

Development. 2004 Oct;131(20):5139-52. doi: 10.1242/dev.01300.


The homeodomain transcription factor Chx10 is one of the earliest markers of the developing retina. It is required for retinal progenitor cell proliferation as well as formation of bipolar cells, a type of retinal interneuron. or(J) (ocular retardation) mice, which are Chx10 null mutants, are microphthalmic and show expanded and abnormal peripheral structures, including the ciliary body. We show here, in a mixed genetic background, the progressive appearance of pigmented cells in the neural retina, concomitant with loss of expression of retinal markers. Fate mapping analysis using a multifunctional Chx10 BAC reporter mouse revealed this process to be direct transdifferentiation of retinal cells into pigmented cells. Microarray and in situ hybridization analyses revealed a complex program underlying the transdifferentiation. This program involved the expansion of expression of genes normally found only in the periphery into central regions of the eye. These genes included a transcription factor controlling pigmentation, Mitf, and the related factor Tfec (Tcfec -- Mouse Genome Informatics), which can activate a melanogenic gene expression program. Misexpression of Chx10 in the developing retinal pigmented epithelium (RPE) caused downregulation of Mitf, Tfec, and associated pigment markers, leading to a nonpigmented RPE. These data link Chx10 and Mitf to maintenance of the neural retina and RPE fates respectively. Further, they suggest a new role for Chx10 in maintenance of compartment boundaries in the peripheral retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Differentiation / physiology
  • Cell Movement / physiology
  • Chick Embryo
  • DNA-Binding Proteins / metabolism
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / metabolism
  • Gene Expression Regulation, Developmental / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Microphthalmia-Associated Transcription Factor
  • Pigmentation / genetics
  • Pigmentation / physiology
  • Retina / cytology
  • Retina / embryology
  • Retina / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Tcfec protein, mouse
  • Transcription Factors
  • Vsx2 protein, mouse