TY - JOUR
T1 - Optix functions as a link between the retinal determination network and the dpp pathway to control morphogenetic furrow progression in Drosophila
AU - Li, Yumei
AU - Jiang, Yuwei
AU - Chen, Yiyun
AU - Karandikar, Umesh
AU - Hoffman, Kristi
AU - Chattopadhyay, Abanti
AU - Mardon, Graeme
AU - Chen, Rui
N1 - Funding Information:
We thank Francesca Pignoni, Hugo Bellen, Peter ten Dijke, Uwe Walldorf, Ilaria Rebay, the Bloomington Stock Center and the Developmental Studies Hybridoma Bank for stocks and antibodies used in this study. This work is supported by funds from the National Eye Institute ( R01EY016853 ) and the Retina Research Foundation Research to R.C. and the National Eye Institute ( EY011232 ) to G.M.
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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.
KW - Dpp
KW - Morphogenic furrow
KW - Optix
KW - Retinal determination network
KW - Retinal development
UR - http://www.scopus.com/inward/record.url?scp=84881550382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881550382&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2013.06.015
DO - 10.1016/j.ydbio.2013.06.015
M3 - Article
C2 - 23792115
AN - SCOPUS:84881550382
SN - 0012-1606
VL - 381
SP - 50
EP - 61
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -