Disrupted retinal development in the embryonic belly spot and tail mutant mouse.
The Belly spot and tail (Bst) semidominant mutation, mapped to mouse Chromosome 16, leads to developmental defects of the eye, skeleton, and coat pigmentation. In the eye, the mutant phenotype is characterized by the presence of retinal colobomas, a paucity of retinal ganglion cells, and axon misrouting. The severity of defects in the Bst/+ retina is variable among individuals and is often asymmetric. In order to determine the role of the Bst locus during retinal morphogenesis, we searched for the earliest observable defects in the developing eye. We examined the retinas of Bst/+ and +/+ littermates from embryonic day 9.5 (E9.5) through E13.5 and measured retinal size, cell density, cell death, mitotic index, and cell birth index. We have found that development of the Bst/+ retina is notably dilatory by as early as E10.5. The affected retinas are smaller than their wildtype counterparts, and optic fissure fusion is delayed. In the mutant, there is a marked lag in the exit of retinal cells from the mitotic cycle, even though there are no observable differences in the rate of cellular proliferation or cell death between the two groups. We hypothesize that Bst regulates retinal cell differentiation and that variability of structural defects in the mutant, such as those affecting optic fissure fusion, is a reflection of the extent of developmental delay brought about by the Bst mutation.
Center for Neuroscience, University of Tennessee Memphis, 855 Monroe Avenue, Memphis, Tennessee, 38163, USA.
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Tang
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Goldowitz
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D005314:Embryonic and Fetal Development; D005123:Eye / Q000196:embryology / Q000254:growth & development*; D005128:Eye Diseases / Q000235:genetics*; D006651:Histocytochemistry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012160:Retina / Q000196:embryology / Q000254:growth & development*