Lhx2links the intrinsic and extrinsic factors that control optic cup formation

Abstract

A crucial step in eye organogenesis is the transition of the optic vesicle into the optic cup. Several transcription factors and extracellular signals mediate this transition, but whether a single factor links them into a common genetic network is unclear. Here, we provide evidence that the LIM homeobox gene Lhx2, which is expressed in the optic neuroepithelium, fulfils such a role. In Lhx2 -/-mouse embryos, eye field specification and optic vesicle morphogenesis occur, but development arrests prior to optic cup formation in both the optic neuroepithelium and lens ectoderm. This is accompanied by failure to maintain or initiate the expression patterns of optic-vesicle-patterning and lens-inducing determinants. Of the signaling pathways examined, only BMP signaling is noticeably altered and Bmp4 and Bmp7 mRNAs are undetectable. Lhx2 -/-optic vesicles and lens ectoderm upregulate Pax2, Fgf15 and Sox2 in response to BMP treatments, and Lhx2 genetic mosaics reveal that transcription factors, including Vsx2 and Mitf, require Lhx2 cell-autonomously for their expression. Our data indicate that Lhx2 is required for optic vesicle patterning and lens formation in part by regulating BMP signaling in an autocrine manner in the optic neuroepithelium and in a paracrine manner in the lens ectoderm. We propose a model in which Lhx2 is a central link in a genetic network that coordinates the multiple pathways leading to optic cup formation.

Transcription Factor SOX9 Plays a Key Role in the Regulation of Visual Cycle Gene Expression in the Retinal Pigment Epithelium

“…LHX2, a member of the LIM homeobox family (21), plays an essential role in early eye development, particularly in the transition of the optic vesicle into the optic cup (22,23). In the retina, Lhx2 expression is detected in the optic vesicle as early as embryonic day 8.5 and throughout the neural retina before birth, but it becomes largely restricted to Müller glia postnatally (22,24).…”

Control of lens development by Lhx2-regulated neuroretinal FGFs

“…But BMP treatment does not rescue the morphology of Lhx2 −/− mutant optic vesicle or surface ectoderm. These findings suggest that BMP signaling partially mediates Lhx2-dependent regulation of optic vesicle and lens vesicle induction (Yun et al, 2009). However, whether Lhx2 is required for lens development beyond lens placode formation is not known.…”

In vivo evidence for unbiased ikaros retinal lineages using an ikaros‐cre mouse line driving clonal recombination

“…This project further asks for lineage data at several intermediate stages of retinogenesis, and these results will be best compared to adult clone composition in the context of a unique and consistent mouse line. There are currently other mouse lines available to achieve sparse Cremediated recombination in the retina (Badea et al, 2009b;Yun et al, 2009;Brzezinski et al, 2011). In these lines, a drug such as tamoxifen is used to activate Cre recombinase activity at a specific time, and limiting dilutions can be applied to restrict recombination to a subset of RPCs.…”