Border-cell migration requires integration of spatial and temporal signals by the BTB protein Abrupt

Abstract

During development, elaborate patterns of cell differentiation and movement must occur in the correct locations and at the proper times. Developmental timing has been studied less than spatial pattern formation and the mechanisms integrating the two are poorly understood. Border cell migration in the Drosophila ovary occurs specifically at stage 9. Timing of the migration is regulated by the steroid hormone ecdysone, whereas spatial patterning of the migratory population requires localized activity of the JAK/STAT pathway. Ecdysone signaling is patterned spatially as well as temporally, although the mechanisms are not well understood. In stage 9 egg chambers, ecdysone signaling is highest in anterior follicle cells including the border cells. We identify the gene abrupt as a repressor of ecdysone signaling and border cell migration. Abrupt protein is normally lost from border cell nuclei during stage 9, in response to JAK/STAT activity. This contributes to the spatial pattern of the ecdysone response. Abrupt attenuates ecdysone signaling via a direct interaction with the bHLH domain of the P160 ecdysone receptor coactivator Taiman (Tai). Together these findings provide a molecular mechanism by which spatial and temporal cues are integrated.

Requirements of Lgl in cell differentiation and motility during Drosophila ovarian follicular epithelium morphogenesis

“…3,4 Numerous studies have shown that the collective and guided border cell migration requires a number of coordinated signaling activities such as JAK/STAT, JNK, PVR pathways and ecdysone signaling etc. [5][6][7][8][9][10][11][12][13][14] In addition, the apico-basal polarity and DE-Cadherin based adhesion are crucial for the integrity of border cell cluster during its morphogenetic movement. 6,15,16 As developmental cell migration and pathological cell invasion involve common cellular and biological processes, 3,10,[17][18][19][20][21] further investigation of this model system will contribute to unraveling the molecular mechanisms underlying cancer invasion and metastasis.…”

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

“…In border cells, signaling through the PDGF/VEGF-related receptor (PVR) and the EGF receptor (EGFR) function together to control their migratory speed and direction McDonald et al 2003McDonald et al , 2006. Other signaling cascades, such as steroid hormones and the Notch pathway, also affect border cell migration (Bai et al 2000;Wang et al 2007;Jang et al 2009). Importantly, homologs of these genes and the same signaling cascades in mammals play roles in regulating cell migration and cancer metastasis (Montell 2003;Naora and Montell 2005;Jang et al 2007), demonstrating the relevance of studies of the Drosophila border cells to cancer biology.…”

The Maf factor Traffic jam both enables and inhibits collective cell migration inDrosophilaoogenesis

“…Strikingly, combined tj knockdown and slbo 2811 RESEARCH ARTICLE Traffic jam in cell migration overexpression could induce precocious BCC migration. This was not observed for BCCs that only overexpress Slbo (Jang et al, 2009;Rørth et al, 2000;Starz-Gaiano et al, 2008) (our own observations). Some of those BCCs with reduced Tj and elevated Slbo were able to complete migration at early-to-mid stage 9, when BCCs have normally only begun migration (Fig.…”

“…9C). Through a not-yet-fully-understood mechanism, which involves the activation of ecdysone signaling (Jang et al, 2009), the Jak/Stat pathway becomes active, and induces the expression of Slbo in the developing BCC. We speculate that this initiation of Slbo expression triggers a shift in the balance of the factors that leads to a homeostatic feedback loop between Tj and Slbo.…”