Disrupted retinal development in the embryonic belly spot and tail mutant mouse

The Belly spot and tail (Bst) semidominant mutation, mapped to mouse Chromo some 16, leads to developmental defects of the eye, skeleton, and coat pigm entation. In the eye, the mutant phenotype is characterized by the presence of retinal colobomas, a paucity of retinal ganglion cells, and axon misrou ting. The severity of defects in the Bst/+ retina is variable among individ uals and is often asymmetric. In order to determine the role of the Bst loc us during retinal morphogenesis, we searched for the earliest observable de fects in the developing eye. We examined the retinas of Bst/+ and +/+ litte rmates from embryonic day 9.5 (E9.5) through E13.5 and measured retinal siz e, cell density, cell death, mitotic index, and cell birth index. We have f ound that development of the Bst/+ retina is notably dilatory by as early a s 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 dea th between the two groups. We hypothesize that Bst regulates retinal cell d ifferentiation and that variability of structural defects in the mutant, su ch as those affecting; optic fissure fusion, is a reflection of the extent of developmental delay brought about by the Bst mutation. (C) 1999 Academic Press.