Purchase this article with an account.
Y.H. Liu, K. Kawai, S. Jiang, F. Zhuang; Msx2 Functions as a Key Regulator of Ocular Development . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3875.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Msx2, a homeodomain transcriptional factor belonging to the msh gene family, has been shown to control the development of the optic vesicle. Our previous studies showed that the forced expression of Msx2 gene resulted in microphthalmia due to the reduction in cell proliferation and increased apoptosis. In this study, we describe here the effect of deletion of the Msx2 gene on the morphogenesis of the eye.
For this investigation, Msx2 null mutant (Msx2–/–) and wild type (WT) embryos as controls at embryonic stages of E11.5, E12.5, E14.5, E16.5, and P0 were used. Specimens including eyes were fixed overnight at 4 ºC in Carnoy (60% Methanol, 30% Chloroform,10% Glacial Acetic Acid) or 4% paraformaldehye. Specimens were embedded in paraffin, and sectioned at 5–8 µm thickness at the frontal plane and/or cross plane which we defined to be parallel to the equator plane of the eye. An anti–CyclinD1 antibody was used to determine the status of proliferation.
Msx2 null embryos (Msx2–/–) exhibit elliptical –shaped eyeballs with an appearance that the developing eye is dorsally and ventrally compressed. The size of the eyeballs was smaller than that of wildtype (WT). The Msx2–/– retina was thicker than that of the WT retina, estimated by the ratio of retinal thickness to the diameter of eyeball. Malformation or dysgenesis of the lens was observed. When the lens is present, the lens failed to detach from the cornea. In the case when the lens failed to mature and thus degenerated, the space that should have been occupied by the lens was now infiltrated by the vasculature. In the mid–ventral portion of the eye, retinal fissure was observed. At this area, the retina caves inward to the center of the eye; retinal cells appeared more packed, and optic nerve fiber layer was thinner than that at other parts of the retina. CyclinD1 positive cells are easily identifiable at the dorsal and especially ventral peripheral edges of the retina around the ventral retinal fissure in contrast to the lack of CyclinD1 immune–reactivity in the peripheral edges of the wild–type retina.
These results support the hypothesis that Msx2 is a key regulator of ocular development. Its function is required for the morphogenesis of the lens and retina. The loss of Msx2 prevents lens maturation and detachment from the cornea. In addition, the Msx2 gene is required for proper cell cycle control in the peripheral retina.
This PDF is available to Subscribers Only