optix functions as a link between the retinal determination network and the dpp pathway to control morphogenetic furrow progression in Drosophila

Abstract

optix, the Drosophila ortholog of the SIX3/6 gene family in vertebrate, encodes a homeodomain protein with a SIX protein-protein interaction domain. In vertebrates, Six3/6 genes are required for normal eye as well as brain development. However, the normal function of optix in Drosophila remains unknown due to lack of loss-of-function mutation. Previous studies suggest that optix is likely to play important role as part of the retinal determination (RD) network. To elucidate normal optix function during retinal development, multiple null alleles for optix have been generated. Loss-of-function mutations in optix result in lethality at the pupae stage. Surprisingly, close examination of its function during eye development reveals that, unlike other members of the RD network, optix is required only for morphogenetic furrow (MF) progression, but not initiation. The mechanisms by which optix regulates MF progression is likely through regulation of signaling molecules in the furrow. Specifically, although unaffected during MF initiation, expression of dpp in the MF is dramatically reduced in optix mutant clones. In parallel, we find that optix is regulated by sine oculis and eyes absent, key members of the RD network. Furthermore, positive feedback between optix and sine oculis and eyes absent is observed, which is likely mediated through dpp signaling pathway. Together with the observation that optix expression does not depend on hh or dpp, we propose that optix functions together with hh to regulate dpp in the MF, serving as a link between the RD network and the patterning pathways controlling normal retinal development.

Shared and distinct mechanisms of atonal regulation in Drosophila ocelli and compound eyes

“…Similarly, in the developing compound eye, Optix is not expressed in the posterior-most region of the eye field, even prior to the start of neurogenesis (Supplementary Fig. S3A), and it is required for the formation of anterior ommatidia but not of several rows of posterior ones (Li et al, 2013). In agreement with these reports, we observed loss of anterior ommatidia and developmental defects when Optix was silenced preferentially in the anterior progenitors of the compound eye field ( tsh-GAL4 UAS-Optix RNAi ) (Supplementary Fig.…”

“…Intriguingly, Optix also displays differences along the anterior-posterior axes of both organs; specifically, it is required in the anterior ocellus and the anterior region of the compound eye, but not for posterior ommatidia and posterior ocelli formation (Fig. S3; Li et al, 2013; Domínguez-Cejudo and Casare, 2015). These parallel differences cast interesting light on the origin of both organs from their shared precursor.…”

The fly eye: Through the looking glass

“…Until recently, it has been assumed that the RD network is primarily tasked with promoting an eye fate. Indeed, several network members are known to participate in retinal cell proliferation, pattern formation, and cell‐fate specification (Pignoni et al, ; Suzuki and Saigo, ; Yan et al, ; Pauli et al, ; Zhang et al, ; Jemc and Rebay, ; Tanaka‐Matakatsu and Du, ; Li et al, ; Weasner and Kumar, ; Karandikar et al, ; Tanaka‐Matakatsu et al, ; Zhu et al, ).…”

Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks

“…Our analysis of the RDGN considered all transcriptional regulators that can induce ectopic eyes when misexpressed in the fly: Ey, Eya, So, Dac, Toy, Teashirt (Tsh), Tiptop (Tio), Eyegone (Eyg), Twin of eyegone (Toe), Optix, Distal antenna (Dan), and Distal antenna-related (Danr) (Bessa et al, 2009; Bonini et al, 1997; Curtiss et al, 2007; Czerny et al, 1999; Datta et al, 2009; Halder et al, 1995; Jang et al, 2003; Li et al, 2013; Pan and Rubin, 1998; Seimiya and Gehring, 2000; Shen and Mardon, 1997; Weasner et al, 2007; Yao et al, 2008). The scoring scheme reaffirmed Ey, Eya, and So as core RDGN members, consistent with the prevailing opinion in the field (Table 1, Figs.…”