Abstract
During mouse eye development, all retinal cell types are generated from the population of retina-committed progenitors originating from the neuroepithelium of the optic vesicle. Conditional gene inactivation provides an efficient tool for studying the genetic basis of the developing retina; however, the number of retina-specific Cre lines is limited. Here we report generation of the mRx-Cre BAC transgenic mouse line in which the expression of Cre recombinase is controlled by regulatory sequences of the mouse Rx gene, one of the earliest determinants of retinal development. When mRx-Cre transgenic mice were crossbred with the ROSA26R or ROSA26R-EYFP reporter lines, the Cre activity was observed in the optic sulcus from embryonic day 8.5 onwards and later in all progenitors residing in the neuroepithelium of the optic cup. Our results suggest that mRx-Cre provides a unique tool for functional genetic studies in very early stages of retinal development. Moreover, since eye organogenesis is dependent on the inductive signals between the optic vesicle and head surface ectoderm, the inductive ability of the optic vesicle can be analyzed using mRx-Cre transgenic mice.
Highlights
Mammalian eye organogenesis is a multistep process of complex morphological events that involves interaction of the forebrainderived optic vesicle (OV) with lens-competent head surface ectoderm (SE). This interaction leads to the coordinated invagination of both OV and SE resulting in formation of the optic cup (OC) [1]
The inner layer of OC is populated by retinal progenitor cells that further differentiate into seven retinal cell types: ganglion cells, amacrine cells, bipolar cells, horizontal cells, cone and rod photoreceptors and Muller glia cells
By E10.5 expression was detected in the neuroepithelium of the optic cup and in the invaginating structure of the lens pit (Figure 2D’)
Summary
Mammalian eye organogenesis is a multistep process of complex morphological events that involves interaction of the forebrainderived optic vesicle (OV) with lens-competent head surface ectoderm (SE). To perform conditional gene inactivation in retinal progenitors, utilization of a few Cre recombinase-expressing mouse lines has been reported. We have taken advantage of the Rx expression and have generated two transgenic mouse lines, MB31-Cre and mRx-Cre, and compared their recombination potential with that of Rx-Cre. Our data demonstrate that among the three analyzed lines, mRx-Cre represents an ideal tool for gene manipulation in early retinal progenitors as judged by its specificity, strength and early onset.
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