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Publication : Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders.

First Author  Melamed David Year  2020
Journal  Elife Volume  9
PubMed ID  33135631 Abstract Text  DrosophilaFollicle Stem Cells (FSCs) by spatially-restricted niche signals. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. We show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC domain, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. Wnt pathway activity declines from the anterior, promotes anterior FSC locations and EC production, and opposes FC production. The pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs and FCs at either end of opposing signaling gradients, and impose a pattern of proliferation that matches derivative production. Adult organisms contain a variety of cells that are routinely replaced using adult stem cells which can generate the cells of a specific tissue. These stem cells are often clustered into small groups, where combinations of chemical signals from nearby cells can encourage each stem cell to divide or ‘differentiate’ into another type of cell. These different signals must somehow balance stem cell division and differentiation to maintain the size and shape of the community. The ovary of an adult fruit fly contains a group of adult stem cells called follicle stem cells, or FSCs for short. FSCs support the continual production of eggs by supplying two types of cell from opposite faces of the stem cell cluster: dividing follicle cells emerge from the back of the cluster and guide late egg development, while non-dividing escort cells come from the front and guide early egg development. Two of the signals that control FSCs are graded over the cluster. JAK-STAT signaling is strongest in the follicle cell territory and gradually declines towards the front, while Wnt signaling is strongest in escort cells and absent from early follicle cells. However, it was unclear how the gradients of these two signals maintain the FSC population and control the formation of follicle and escort cells. To answer this question, Melamed and Kalderon used genetic engineering to modify the strength of these two signals. The experiments measured how this affected the rate at which FSCs divide and are converted into follicle or escort cells. Melamed and Kalderon found that the strength of JAK-STAT signaling dictated division rates, which may explain why the rate cells divide varies across the FSC cluster and escort cells do not divide at all. JAK-STAT signaling also stimulated FSCs to become follicle cells and opposed their conversion to escort cells. Conversely, stronger Wnt signaling favored the production of...
Doi  10.7554/eLife.61204 Month  11

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