The physical contact of optic vesicle with head surface ectoderm is an initial event triggering eye morphogenesis. This interaction leads to lens specification followed by coordinated invagination of the lens placode and optic vesicle, resulting in formation of the lens, retina and retinal pigmented epithelium. Although the role of Pax6 in early lens development has been well documented, its role in optic vesicle neuroepithelium and early retinal progenitors is poorly understood. Here we show that conditional inactivation of Pax6 at distinct time points of mouse neuroretina development has a different impact on early eye morphogenesis. When Pax6 is eliminated in the retina at E10.5 using an mRx-Cre transgene, after a sufficient contact between the optic vesicle and surface ectoderm has occurred, the lens develops normally but the pool of retinal progenitor cells gradually fails to expand. Furthermore, a normal differentiation program is not initiated, leading to almost complete disappearance of the retina after birth. By contrast, when Pax6 was inactivated at the onset of contact between the optic vesicle and surface ectoderm in Pax6Sey/flox embryos, expression of lens-specific genes was not initiated and neither the lens nor the retina formed. Our data show that Pax6 in the optic vesicle is important not only for proper retina development, but also for lens formation in a non-cell-autonomous manner.
KEY WORDS: Pax6, Retinal progenitor, mRx-Cre, Lens induction
INTRODUCTIONProper eye development is dependent on the coordinated formation of two main tissues in the eye: the retina and the lens. Vertebrate eye development begins with invagination of the optic vesicle (OV) toward the lens-competent head surface ectoderm (SE). As OV contacts SE, a series of reciprocal inductive signals elicit formation of the lens placode (LP) and subsequent invagination of both LP and OV to form a two-layered optic cup (OC), with retinal pigmented epithelium (RPE) surrounding the retina (reviewed by Fuhrmann, 2010; Chow and Lang, 2001;Ogino et al., 2012). Genetic studies have identified multiple transcription factors and signaling pathways interacting in a complex network orchestrating early eye development (reviewed by Fuhrmann, 2010; Chow and Lang, 2001;Ogino et al., 2012;Xie and Cvekl, 2011). Among the signaling pathways, BMP (Furuta and Hogan, 1998;Rajagopal et al., 2009;Sjödal et al., 2007;Wawersik et al., 1999) and FGF (Faber et al., 2001;Garcia et al., 2011;Gotoh et al., 2004;Pan et al., 2006) were found to be essential for lens induction and coordinated OV-to-OC transition, as severe eye defects are associated with their inactivation.
RESEARCH ARTICLEInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14420 Prague 4, Czech Republic. At the time the LP is formed, the dorsal region of the OV becomes specified to the retina and is populated with mitotically active retinal progenitor cells (RPCs) (Fuhrmann, 2010;Levine and Green, 2004). Lineage-tracing studies have shown that RPCs a...