At the crossroads of differentiation and proliferation: Precise control of cell‐cycle changes by multiple signaling pathways in Drosophila follicle cells

Abstract

Here, we discuss the findings to date about genes and pathways required for regulation of somatic follicle-cell proliferation and differentiation during Drosophila oogenesis and demonstrate how loss of these genes contributes to the tumorigenic potential of mutant cells. Follicle cells undergo cell-fate determination through stepwise activation of multiple signaling pathways, including the Notch, Hedgehog, Wingless, janus kinase/STAT, and JNK pathways. In addition, changes in DNA replication and cellular growth depend on the spatial and temporal activation of the mitotic cycle-endocycle and endocycle-gene amplification cell-cycle switches and insulin-dependent monitoring of cellular health; systemic loss of these pathways contributes to loss of controlled cellular proliferation, loss of differentiation/growth, and aberrant cell polarity in follicle cells. We also highlight the effects of the neoplastic and Hippo pathways on the cell cycle and cellular proliferation in promoting normal development and conclude that lack of coordination of multiple signaling pathways promotes conditions favorable for tumorigenesis.

A novel mitochondrial pool of Cyclin E, regulated by Drp1, is linked to cell density dependent cell proliferation

“…By contrast, the Drosophila PFCs having lower mtCycE (Fig. 1F) and higher Drp1 activity differentiate under the influence of EGFR-MEK-ERK signaling (Klusza and Deng, 2011;Mitra et al, 2012).…”

“…This concept explains why the Drosophila MBCs with elevated mtCycE (Fig. 1F) and reduced Drp1 activity only differentiate in the absence of EGFR-MEK-ERK signaling (Klusza and Deng, 2011;Mitra et al, 2012), which would otherwise release the mtCycE pool to aberrantly maintain cell proliferation and prevent differentiation. By contrast, the Drosophila PFCs having lower mtCycE (Fig.…”

“…The early follicle cells, after differentiating from the lineage-specific stem cells, undergo mitotic divisions during developmental stages 1 through 6. After stage 6, the follicle cells exit the mitotic cycle to terminally differentiate into the epithelial cell layer, which is further patterned into various cell types (Klusza and Deng, 2011). We have previously reported differential mitochondrial regulation in the mitotic follicle cells and the differentiated-patterned main body follicle cells (MBCs) and posterior follicle cells (PFCs) (Mitra et al, 2012).…”

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

“…The follicular epithelium, with two clear global changes in cellcycle programs and differentiation status, has served as an excellent model in the study of developmental switches (reviewed by Klusza and Deng, 2011). The rise and fall (activation and downregulation) of Notch signaling in the follicle cells have direct effects on the two developmental switches.…”

“…In some cancerous and differentiated cells, however, this rule is broken and DNA is copied without cell division. The Drosophila egg chamber, the developmental unit of oogenesis, is an excellent model system in which to study how developmental signals control different DNA-replication and cellcycle patterns (Dobens and Raftery, 2000;Klusza and Deng, 2011). During oogenesis, the somatically derived follicle cells undergo mitosis until stage 6 followed by three rounds of endocycling, during which they replicate their genomic contents without division.…”