title: 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 an 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77303, USA.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Chen
authors.forename: Umesh
authors.initials: U
authors.lastname: Karandikar
authors.forename: Kristi
authors.initials: K
authors.lastname: Hoffman
authors.forename: Abanti
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Graeme
authors.initials: G
authors.lastname: Mardon
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D012160:Retina / Q000196:embryology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C409102:Optix protein, Drosophila; D014157:Transcription Factors; C064196:dpp protein, Drosophila; C077245:hh protein, Drosophila
keywords: Morphogenic furrow; Retinal determination network; Retinal development; dpp; optix