Drosophilafollicle cells are patterned by multiple levels of Notch signaling and antagonism between the Notch and JAK/STAT pathways

Abstract

The specification of polar, main-body and stalk follicle cells in the germarium of the Drosophila ovary plays a key role in the formation of the egg chamber and polarisation of its anterior-posterior axis. High levels of Notch pathway activation, resulting from a germline Delta ligand signal, induce polar cells. Here we show that low Notch activation levels, originating from Delta expressed in the polar follicle cells, are required for stalk formation. The metalloprotease Kuzbanian-like, which cleaves and inactivates Delta, reduces the level of Delta signaling between follicle cells, thereby limiting the size of the stalk. We find that Notch activation is required in a continuous fashion to maintain the polar and stalk cell fates. We further demonstrate that mutual antagonism between the Notch and JAK/STAT signaling pathways provides a crucial facet of follicle cell patterning. Notch signaling in polar and main-body follicle cells inhibits JAK/STAT signaling by preventing STAT nuclear translocation, thereby restricting the influence of this pathway to stalk cells. Conversely, signaling by JAK/STAT reduces Notch signaling in the stalk. Thus, variations in the levels of Notch pathway activation, coupled with a continuous balance between the Notch and JAK/STAT pathways, specify the identity of the different follicle cell types and help establish the polarity of the egg chamber.

Midkine induces epithelial-mesenchymal transition through Notch2/Jak2-Stat3 signaling in human keratinocytes

“…[37][38][39][40] Furthermore, previous reports showed that Notch expression in mouse embryonic dental mesenchyme is upregulated by retinoic acid, a specific inducer of MK transcription. 10,11 In addition, Jak2 was found to modulate cell-cell adhesion in epithelial cells and EMT, which occurs during malignant development.…”

“…24,59 Therefore, we suggest that the MK-Notch2-Stat3 pathway contributes to EMT, which is one of the important component of neonatal and tumor development. [5][6][7][8][9][10]31,[37][38][39][40][60][61][62][63] Since EMT plays a specific role in the migration of cells from a primary tumor into the circulation [1][2][3][4] an improved understanding of the role of MK-Notch2-Stat3 signaling in the EMT may provide a rationale for developing additional targeted cancer therapies. incubated with yeast extracts (100 μg) expressing the pGal4-ADNotch2 fusions tagged with HA-epitope.…”

“…26,[34][35][36] Recent reports showed that the Notch and Jak-Stat signaling pathways are tightly involved in growth and differentiation regulation of many cells. [37][38][39][40] In cortical neuroepithelial cells, Notch downstream intermediates, Hes1 and Hes5, were shown to associate with Stat3, promoting the phosphorylation of the latter, while suppression of Hes1 levels reduced Stat3 phosphorylation. 38 To further investigate these pathways in keratinocytes, we co-precipitated endogenous Hes1/Stat3 protein complexes from nuclear lysates of HaCaT cells grown in the presence or absence of MK using antibodies against Hes1.…”

Drosophila Pur-α binds to trinucleotide-repeat containing cellular RNAs and translocates to the early oocyte

“…Specification of these polar cells depends on a relay of Notch and JAK/STAT signaling between subsequent germ line cysts as they bud out of the germarium. 23,24 Drosophila Pur-α is part of mRNP transport complexes. Our results indicate that Pur-α may participate in the transport of mRNAs into the growing oocyte.…”

The microRNA miR-7 regulates Tramtrack69 in a developmental switch in Drosophila follicle cells

“…2A). In addition, the expression of two other Notch reporters, Gbe-lacZ (Furriols and Bray, 2001) and m7-lacZ (Assa-Kunik et al, 2007), remained unchanged in follicle cells with miR-7 overexpression (data not shown), indicating that miR-7 does not regulate Notch activity [NICD/Su(H) mediated activation] in follicle cells. In addition to Notch, our previous findings have demonstrated that the EcR pathway also regulates the E/A switch (Sun et al, 2008).…”