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R.A. Poche, M.A. Raven, K.M. Kwan, Y. Furuta, B.E. Reese, R.R. Behringer; LIM–Homeodomain Transcription Factor Lim1 (Lhx1) Regulates the Migration of Retinal Horizontal Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2776.
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Homeodomain transcription factors are known to have essential roles in retinal cell–fate determination and subsequent differentiation. It has been proposed that these transcription factors function, in a combinatorial code, to pattern the seven retinal cell classes derived from a common progenitor pool. To further define the importance of a combinatorial transcription factor network to retinal development, we are characterizing the role of the homeodomain transcription factor Lim1 (Lhx1). Beginning at embryonic day 15.5 and continuing into adulthood, Lim1 is expressed in horizontal cells of the mouse retina. The spatial and temporal expression of Lim1 suggests that Lim1 may have a role in regulating horizontal cell precursor migration to the mature horizontal cell layer.
In order to circumvent the embryonic lethality of the Lim1 null mutant, mice homozygous for a Lim1 floxed allele were crossed to transgenic mice expressing a retina–specific Cre recombinase thereby generating retina–specific knockouts.
Conditional knockout retinas show a change in cell positioning whereby cells, normally fated to become horizontal cells, are ectopically localized to the inner aspects of the inner nuclear layer, many being positioned at the border of the inner plexiform layer. Previous studies in chick suggest that horizontal cells migrate bi–directionally, from the ventricular zone then to the vitreal side of the neuroepithelium, before migrating back again to their final laminar position in the inner nuclear layer adjacent to the outer plexiform layer. In the conditional mutant retinas, Lim1–/– horizontal cells are apparently incapable of initiating or completing the second phase of migration to the prospective horizontal cell layer and remain "stuck" amongst the amacrine cells where they continue to differentiate, extending their processes basally into the inner plexiform layer. Thus, the new local environment is possibly influencing the ectopic cell morphology.
Based on the normal expression of Lim1 throughout the process of horizontal cell migration, and on the conditional knockout phenotype, we propose that Lim1 regulates the second phase of horizontal cell bi–directional migration.
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