Dorsal retinal pigment epithelium differentiates as neural retina in the microphthalmia (mi/mi) mouse.
OBJECTIVE
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.
Bumsted
K M
KM
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut, USA.
Barnstable
C J
CJ
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D016350:Leucine Zippers / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D051739:Microphthalmia-Associated Transcription Factor; D008850:Microphthalmos / Q000235:genetics / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051857:Otx Transcription Factors; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors