The Hippo pathway controls polar cell fate through Notch signaling during Drosophila oogenesis

Abstract

During Drosophila oogenesis, the somatic follicle cells form an epithelial layer surrounding the germline cells to form egg chambers. In this process, follicle cell precursors are specified into polar cells, stalk cells, and main-body follicle cells. Proper specification of these three cell types ensures correct egg chamber formation and polarization of the anterior-posterior axis of the germline cells. Multiple signaling cascades coordinate to control the follicle cell fate determination, including Notch, JAK/STAT, and Hedgehog signaling pathways. Here, we show that the Hippo pathway also participates in polar cell specification. Over-activation of yorkie (yki) leads to egg chamber fusion, possibly through attenuation of polar cell specification. Loss-of-function experiments using RNAi knockdown or generation of mutant clones by mitotic recombination demonstrates that reduction of yki expression promotes polar cell formation in a cell-autonomous manner. Consistently, polar cells mutant for hippo (hpo) or warts (wts) are not properly specified, leading to egg chamber fusion. Furthermore, Notch activity is increased in yki mutant cells and reduction of Notch activity suppresses polar cell formation in yki mutant clones. These results demonstrate that yki represses polar cell fate through Notch signaling. Collectively, our data reveal that the Hippo pathway controls polar cell specification. Through repressing Notch activity, Yki serves as a key repressor in specifying polar cells during Drosophila oogenesis.

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

“…Furthermore, border cell clusters containing hpo or wts mutant polar cells and wild-type outer border cells have never been obtained (Figure 1). This phenomenon can be explained by our previous findings that the Hippo pathway is involved in polar cell determination (Chen et al 2011). The Hippo pathway is critical to promote polar cell fate by suppressing Notch signaling during early oogenesis.…”

“…Although YAP has been demonstrated to induce EMT and cell migration in cultured cells (Zhao et al 2008a;Zhang et al 2009;Xu et al 2011), migration of border cell clusters containing yki B5 mutant outer border cells was normal compared with that in the FRT42D control 3 days after clone induction ( Figure 1, G, H, and L), indicating that yki in outer border cells is not required for border cell migration. We did not examine yki mutant clones for border cell migration at day 6 after clone induction because most yki mutant cells differentiated into polar cells at day 6 as reported previously (Chen et al 2011). …”

“…During cell fate determination in early oogenesis, the Hippo pathway promotes polar cell fate. Therefore, mutation of hpo or wts suppresses polar cell formation (Chen et al 2011). Once polar cells are determined, the Hippo pathway suppresses proliferation of polar cells.…”

“…When wts was knocked down or yki was overexpressed with upd-Gal4, 5-15 Fas3-positive cells were observed (Figure 3, C, J, K, and M). Since our previous study has demonstrated that the Hippo pathway controls polar cell fate during early oogenesis (Chen et al 2011), it is crucial to examine whether modulation of the Hippo pathway disrupts polar cell fate determination, which in turn attenuates border cell migration. While there were usually two polar cells at the anterior end of an egg chamber (Figure 4, A, D, and F), knockdown of wts with upd-Gal4 led to more than two cells expressing polar cells markers PZ80-lacZ (a lacZ insertion in Fas3) and A101-lacZ (a lacZ insertion in neur) ( Figure 4, A-E).…”

Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

“…In line with its function, Yki is predominantly expressed in somatic cells in germaria, including ECs [37] (Supplementary information, Figure S1A-S1A). This is similar to the expression pattern of Ci (Supplementary information, Figure S4A-S4A″) [38], the key transcriptional effector in the Hh signaling pathway.…”