JAK/STAT signaling promotes regional specification by negatively regulatingwinglessexpression inDrosophila

Abstract

During development, a small number of conserved signaling molecules regulate regional specification, in which uniform populations of cells acquire differences and ultimately give rise to distinct organs. In the Drosophila eye imaginal disc, Wingless (Wg) signaling defines the region that gives rise to head tissue. JAK/STAT signaling was thought to regulate growth of the eye disc but not pattern formation. However, we show that the JAK/STAT pathway plays an important role in patterning the eye disc: it promotes formation of the eye field through repression of the wg gene. Overexpression of the JAK/STAT activating ligand Unpaired in the eye leads to loss of wg expression and ectopic morphogenetic furrow initiation from the lateral margins. Conversely, tissue lacking stat92E, which cannot transduce JAK/STAT signals, is transformed from retinal tissue into head cuticle, a phenotype that is also observed with ectopic Wg signaling. Consistent with this, cells lacking stat92E exhibit ectopic wg expression. Conversely, wg is autonomously repressed in cells with hyperactivated Stat92E. Furthermore, we show that the JAK/STAT pathway regulates a small enhancer in the wg 3Ј cis genomic region. As this enhancer is devoid of Stat92E-binding elements, we conclude that Stat92E represses wg through another, as yet unidentified factor that is probably a direct target of Stat92E. Taken together, our study is the first to demonstrate a role for the JAK/STAT pathway in regional specification by acting antagonistically to wg.

Retinal Axon Guidance Requires Integration of Eya and the Jak/Stat Pathway into Phosphotyrosine-Based Signaling Circuitries in Drosophila

“…Eya RNAi (Figure 4, B and F), suggesting endogenous signaling is limited and insufficient to activate the extra Stat protein. Consistent with this interpretation, previous reports have shown that although UAS-Stat can rescue Stat92E null phenotypes, its overexpression in an otherwise wild-type background does not perturb eye development (Ekas et al 2006).…”

Wingless Signaling in Drosophila Eye Development

“…Another regulator of wg expression is the JAK/STAT signaling pathway. The ligand Unpaired (Upd) is expressed at the posterior margin of the early eye disc and promotes the formation of the eye field through repression of wg transcription (37,38). The negative regulatory interactions between anteriorly expressed Wg and posteriorly expressed signaling molecules including Hh, Dpp and Upd thus define the boundaries of the eye field.…”

New Advances in Signaling and Pattern Formation

“…A presentation as well as a recent paper from Erika Bach's laboratory concentrated specifically on a developmental patterning role for Upd through the Jak/Stat pathway. 8 They suggest a role for Jak/Stat in establishing the proximal-distal axis in the developing leg and antennal imaginal discs. They show that Upd is expressed in a pattern complementary to Wingless expression.…”

“…Furthermore, they have shown that in the developing eye imaginal disc Jak/Stat has a patterning function in addition to the previously identified effects on cell proliferation. 8 In addition, they have found that an as yet unidentified cell-autonomous factor functions downstream of Stat to repress Wg expression in imaginal discs. This study implies that much remains to be learned about Jak/Stat signaling in development, and suggests that-by conveying contextspecific signals for stemness, proliferation or differentiation-Jak/Stat is not different from other developmental pathways.…”

“…The site for the latest installment of the Drosophila Research Conference (March [7][8][9][10][11]2007) was downtown Philadelphia. The conference offered an illustration of all that is great about the Drosophila field bringing together evolutionary biologists, immunologists and everyone in between.…”