Fig. 7.

Schematic representation of reported interactions between factors associated with Peters anomaly. The genes implicated in PA based on previous reports as well as this study are marked in bold. PITX2 and FOXC1 have been shown to physically bind and modulate the activity of each other (Acharya et al. 2011) as well as to be regulated by TGFβ (Silla et al. 2014; Iwao et al. 2009), WNT and retinoic acid signaling pathways (Gage and Zacharias 2009; Kumar and Duester 2010; Hatou et al. 2013); in connection with the WNT pathway, PITX2 has been reported to physically bind the DKK2 promoter (Gage and Zacharias 2009). Also, PITX2 has been shown to regulate the deposition of collagens by regulating the procollagen lysyl hydroxylase gene (Hjalt et al. 2001). B3GLCT is a glucosyltransferase which catalyzes the addition of glucose to O-linked fucose via a β-1,3 linkage onto trombospondin type 1 repeats which have been found in the ADAMTS family of proteins (Ricketts et al. 2007; Wang et al. 2009); some ADAMTS proteins have been shown to cleave heparan sulfate proteoglycans (HSPGs) (Barbouri et al. 2014; Kuno and Matsuhima 1998) and thus potentially affect TGFβ signaling (Lin 2004; Iwao et al. 2009). NDP represents a WNT ligand (Ohlmann and Tamm 2012). TFAP2A has been shown to be responsive to retinoic acid, to inhibit the WNT pathway (Li and Dashwood 2004) and be involved in PITX2 regulation (Bamforth et al. 2004). PAX6 deficiency has been shown to negatively affect FOXE3 (Blixt et al. 2007) and PITX3 expression (Chauhan et al. 2002); PITX3 has been reported to directly regulate FOXE3 expression (Shi et al. 2006; Ahmad et al. 2013). PAX6 and TFAP2A have been demonstrated to physically interact and promote transcription of some corneal genes (Sivak et al. 2004). CYP1B1 participates in the synthesis of retinoic acid (Chambers et al. 2007). FLNA appears to negatively regulate FOXC1 by physical binding and sequestering it to heterochromatin and is important for SMAD translocation into the nucleus (Berry et al. 2005; Huang et al. 2009). FLNA may also be important in maintaining appropriate levels of WNT signaling (Adams et al. 2012)