Dorsal retinal pigment epithelium differentiates as neural retina in the microphthalmia (mi/mi) mouse

Invest Ophthalmol Vis Sci. 2000 Mar;41(3):903-8.


Purpose: Microphthalmia, a bHLH-zip transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigment epithelial (RPE) compartment during optic vesicle and optic cup development. To determine a role for microphthalmia (mi) during eye development, the effects of an mi loss of function mutation on RPE and neural retinal were investigated in the mi/mi mouse.

Methods: A series of embryonic and postnatal mi/mi and wild-type eyes were sectioned and labeled with neural retina- and RPE cell type-specific antibodies. Photoreceptor loss was quantified by counting the number of photoreceptor nuclei spanning the outer nuclear layer throughout postnatal retinal development.

Results: Early neural retinal differentiation is not affected in the mi/mi mouse. The mi/mi ventral retinal pigment epithelial layer begins to develop normally, but does not pigment or attain a differentiated cuboidal morphology. The dorsal region of mi/mi retinal pigment epithelium expands and forms an ectopic retina, which develops all major retinal cell types along a similar time course as the wild type. After birth, mi/mi photoreceptors begin to form rosettes, outer segments fail to elongate, and over an extended time period, the retina degenerates.

Conclusions: Together these results suggest that early retinal development can proceed normally in the mi/mi mutant, but later retinal histogenesis is dependent on the presence of a differentiated retinal pigment epithelium. Most importantly, loss of mi function permits a change in cell fate from RPE to retina in the dorsal eye.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Leucine Zippers / genetics
  • Mice
  • Mice, Mutant Strains
  • Microphthalmia-Associated Transcription Factor
  • Microphthalmos / genetics
  • Microphthalmos / pathology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Otx Transcription Factors
  • Photoreceptor Cells, Vertebrate / pathology
  • Pigment Epithelium of Eye / embryology
  • Pigment Epithelium of Eye / growth & development
  • Pigment Epithelium of Eye / metabolism
  • Pigment Epithelium of Eye / pathology*
  • Retina / embryology
  • Retina / growth & development
  • Retina / metabolism
  • Retina / pathology*
  • Retinal Degeneration / pathology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Nerve Tissue Proteins
  • Otx Transcription Factors
  • Trans-Activators
  • Transcription Factors